Is MYO7A p.Val1669Ile (c.5005G>A) pathogenic?

MYO7A p.Val1669Ile (c.5005G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-18). AlphaMissense: likely benign (0.12); Rare (popmax 0.203%, eas); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Val1669Ile (c.5005G>A)?

MYO7A p.Val1669Ile (c.5005G>A) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Val1669Ile (c.5005G>A) in the general population?

MYO7A p.Val1669Ile (c.5005G>A) is rare (popmax 0.203%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Val1669Ile (c.5005G>A)?

AlphaMissense predicts likely benign (score 0.12) — an in-silico prediction, not a clinical call.

MYO7A p.Val1669Ile

c.5005G>A · rs374655803 · VCV762896

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.12 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.203%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.12	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -5.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.54	donor loss, 5 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.7	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 0.203% East Asian · 91/44,868 alleles

Filtering AF 0.169% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.157%

Overall 0.00954% 154/1,613,856 alleles · rare exomes 117/1,461,572 · genomes 37/152,284 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.203%	493
Remaining individualsnot grpmax-eligible	0.024%	4,166
African / African-American	0.024%	4,169
South Asian	0.0165%	6,072
Admixed American	0.00333%	30,004
Finnishnot grpmax-eligible	0.00313%	31,974
European (non-Finnish)	0.000932%	107,259

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.Val1669Ile
Coding: c.5005G>A
MANE Select: NM_000260
dbSNP: rs374655803
Type: single nucleotide variant
Location: chr11:77201600 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1669: the sh3 domain

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

Disease context

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

Similar variants

MYO7A p.Val1669Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Val1669= Likely benign ★ 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

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-val1669ile (accessed [today's date]).

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