Is MYO7A p.Ile2141Val (c.6421A>G) pathogenic?

MYO7A p.Ile2141Val (c.6421A>G) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-09-09). AlphaMissense: likely benign (0.1264); Ultra-rare (popmax 0.0161%, afr); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Ile2141Val (c.6421A>G)?

MYO7A p.Ile2141Val (c.6421A>G) is associated with Inborn genetic diseases, autosomal dominant nonsyndromic hearing loss 11, Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Ile2141Val (c.6421A>G) in the general population?

MYO7A p.Ile2141Val (c.6421A>G) is ultra-rare (popmax 0.0161%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Ile2141Val (c.6421A>G)?

AlphaMissense predicts likely benign (score 0.1264) — an in-silico prediction, not a clinical call.

MYO7A p.Ile2141Val

c.6421A>G · rs761164010 · VCV1032274

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1264 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0161%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1264	likely benign
REVEL	0.467	indeterminate
SaProt	LLR -6.91	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.14	GERP 1.8, phastCons 0.002
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	23.1	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 0.0161% African / African-American · 12/74,368 alleles

Filtering AF 0.00928% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00727%

Overall 0.000822% 13/1,582,158 alleles · ultra-rare exomes 3/1,429,920 · genomes 10/152,238 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0161%	6,197
Admixed American	0.0018%	55,444

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.Ile2141Val
Coding: c.6421A>G
MANE Select: NM_000260
dbSNP: rs761164010
Type: single nucleotide variant
Location: chr11:77213018 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 2141: the ferm 2 domain; a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

MYO7A p.Ile2141= 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
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-ile2141val (accessed [today's date]).

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