Is MYO7A p.Arg120Ser (c.358C>A) pathogenic?

MYO7A p.Arg120Ser (c.358C>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-04-30). AlphaMissense: ambiguous (0.4728); Ultra-rare (popmax 0.0267%, eas); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Arg120Ser (c.358C>A)?

MYO7A p.Arg120Ser (c.358C>A) is associated with Inborn genetic diseases, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Arg120Ser (c.358C>A) in the general population?

MYO7A p.Arg120Ser (c.358C>A) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Arg120Ser (c.358C>A)?

AlphaMissense predicts ambiguous (score 0.4728) — an in-silico prediction, not a clinical call.

MYO7A p.Arg120Ser

c.358C>A · rs397516302 · VCV43213

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

ambiguous

0.4728 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4728	ambiguous
REVEL	0.651	pathogenic-leaning
SaProt	LLR -7.49	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.5	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 0.0267% East Asian · 12/44,868 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00093% 15/1,613,420 alleles · ultra-rare exomes 12/1,461,054 · genomes 3/152,366 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,739
Remaining individualsnot grpmax-eligible	0.0032%	31,233
European (non-Finnish)	8.48e-05%	1,179,682

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.Arg120Ser
Coding: c.358C>A
MANE Select: NM_000260
dbSNP: rs397516302
Type: single nucleotide variant
Location: chr11:77155979 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 120: the myosin motor domain

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: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 2 Usher syndrome type 1B

Similar variants

MYO7A p.Arg120Cys Uncertain significance ★ ⚠ same residue
MYO7A p.Arg120His Conflicting classifications of pathogenicity ★ ⚠ 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-arg120ser (accessed [today's date]).

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