Is MYO7A p.Lys268Arg (c.803A>G) pathogenic?

MYO7A p.Lys268Arg (c.803A>G) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0659); Rare (popmax 0.198%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Lys268Arg (c.803A>G)?

MYO7A p.Lys268Arg (c.803A>G) is associated with autosomal recessive nonsyndromic hearing loss 2, Usher syndrome type 1, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Lys268Arg (c.803A>G) in the general population?

MYO7A p.Lys268Arg (c.803A>G) is rare (popmax 0.198%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.Lys268Arg (c.803A>G)?

AlphaMissense predicts likely benign (score 0.0659) — an in-silico prediction, not a clinical call.

MYO7A p.Lys268Arg

c.803A>G · rs184866544 · VCV178477

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0659 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.198%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autosomal recessive nonsyndromic hearing loss 2

Computational evidence

Protein change
AlphaMissense	0.0659	likely benign
REVEL	0.497	indeterminate
SaProt	LLR -5.68	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.065	GERP -0.36, phastCons 0.056
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	15.39	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 0.198% European (non-Finnish) · 2,332/1,179,192 alleles

Filtering AF 0.191% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.188%

Overall 0.155% 2,498/1,612,318 alleles · rare exomes 2,354/1,459,998 · genomes 144/152,320 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.198%	506
Remaining individualsnot grpmax-eligible	0.101%	991
Ashkenazi Jewishnot grpmax-eligible	0.0845%	1,183
Admixed American	0.0669%	1,496
African / African-American	0.0307%	3,262
Finnishnot grpmax-eligible	0.0235%	4,261

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.Lys268Arg
Coding: c.803A>G
MANE Select: NM_000260
dbSNP: rs184866544
Type: single nucleotide variant
Location: chr11:77157346 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 268: the myosin motor domain

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

Disease context

autosomal recessive nonsyndromic hearing loss 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

MYO7A p.Lys268Ter Likely pathogenic ★ 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-lys268arg (accessed [today's date]).

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