Is MYO7A p.Arg212His (c.635G>A) pathogenic?

MYO7A p.Arg212His (c.635G>A) is classified Pathogenic/Likely pathogenic in MYO7A (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-07-17). AlphaMissense: likely pathogenic (0.9916); Very rare (popmax 0.00329%, sas); Associated with MYO7A-related disorder.

What condition is associated with MYO7A p.Arg212His (c.635G>A)?

MYO7A p.Arg212His (c.635G>A) is associated with MYO7A-related disorder, retinal disorder, Usher syndrome type 1 (ClinVar).

How common is MYO7A p.Arg212His (c.635G>A) in the general population?

MYO7A p.Arg212His (c.635G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about MYO7A p.Arg212His (c.635G>A)?

AlphaMissense predicts likely pathogenic (score 0.9916) — an in-silico prediction, not a clinical call.

MYO7A p.Arg212His

c.635G>A · rs28934610 · VCV11850

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

AlphaMissense

likely pathogenic

0.9916 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MYO7A-related disorder

Computational evidence

Protein change
AlphaMissense	0.9916	likely pathogenic ✓ concordant with ClinVar
REVEL	0.898	moderately pathogenic-leaning
SaProt	LLR -13.24	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	33.0	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 0.00329% South Asian · 3/91,094 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.0013% 21/1,613,916 alleles · very rare exomes 19/1,461,682 · genomes 2/152,234 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,365
East Asian	0.00223%	44,892
Admixed American	0.00167%	60,014
Remaining individualsnot grpmax-eligible	0.0016%	62,464
Finnishnot grpmax-eligible	0.00156%	64,000
African / African-American	0.00133%	74,940
European (non-Finnish)	0.0011%	90,762

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.Arg212His
Coding: c.635G>A
MANE Select: NM_000260
dbSNP: rs28934610
Type: single nucleotide variant
Location: chr11:77156904 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 212: the myosin motor domain; a UniProt-annotated variant site (in ush1b)

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

Disease context

MYO7A-related disorder

Also linked: retinal disorder Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 2 inherited retinal dystrophy Usher syndrome Usher syndrome type 1B

Similar variants

MYO7A p.Arg212Cys Pathogenic/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-arg212his (accessed [today's date]).

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