Is MYO7A p.Val679Ile (c.2035G>A) pathogenic?

MYO7A p.Val679Ile (c.2035G>A) is classified Benign/Likely benign in MYO7A (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0858); Common (popmax 6.02%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Val679Ile (c.2035G>A)?

MYO7A p.Val679Ile (c.2035G>A) is associated with Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How is Usher syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MYO7A p.Val679Ile (c.2035G>A)?

AlphaMissense predicts likely benign (score 0.0858) — an in-silico prediction, not a clinical call.

MYO7A p.Val679Ile

Q: How common is MYO7A p.Val679Ile (c.2035G>A) in the general population?

MYO7A p.Val679Ile (c.2035G>A) is common (popmax 6.02%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2035G>A · rs35641839 · VCV43170

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.0858 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.02%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Usher syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.0858	likely benign
REVEL	0.32	indeterminate
SaProt	LLR -6.10	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 0.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.02% African / African-American · 4,521/75,040 alleles

Filtering AF 5.88% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.82%

Overall 0.322% 5,194/1,613,706 alleles · common exomes 2,569/1,461,380 · genomes 2,625/152,326 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.02%	17
Admixed American	0.423%	236
Remaining individualsnot grpmax-eligible	0.355%	281
Middle Eastern	0.313%	319
South Asian	0.0154%	6,505
European (non-Finnish)	0.0137%	7,283
East Asian	0.00223%	44,880
Finnishnot grpmax-eligible	0.00157%	63,752

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MYO7A
Protein: p.Val679Ile
Coding: c.2035G>A
MANE Select: NM_000260
dbSNP: rs35641839
Type: single nucleotide variant
Location: chr11:77174855 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 679: the myosin motor domain; a UniProt-annotated variant site (in)

Full MYO7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Usher syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive nonsyndromic hearing loss 2 autosomal dominant nonsyndromic hearing loss 11 Usher syndrome type 1B

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

MYO7A p.Val679Ala Uncertain significance ★★ ⚠ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same condition
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Arg668Cys Pathogenic ★★★ same condition
MYO7A p.Arg853His Likely pathogenic ★★★ same condition
MYO7A p.Glu968Asp Likely pathogenic ★★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/myo7a-p-val679ile (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown