Is MYO7A p.Arg244His (c.731G>A) pathogenic?

MYO7A p.Arg244His (c.731G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-16). AlphaMissense: likely benign (0.1207); Ultra-rare (popmax 0.0565%, nfe); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Arg244His (c.731G>A)?

MYO7A p.Arg244His (c.731G>A) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Arg244His (c.731G>A) in the general population?

MYO7A p.Arg244His (c.731G>A) is ultra-rare (popmax 0.0565%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.Arg244His (c.731G>A)?

AlphaMissense predicts likely benign (score 0.1207) — an in-silico prediction, not a clinical call.

MYO7A p.Arg244His

c.731G>A · rs121965081 · VCV289999

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.1207 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0565%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.1207	likely benign
REVEL	0.632	indeterminate
SaProt	LLR -6.61	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.8	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 0.0565% European (non-Finnish) · 666/1,179,286 alleles

Filtering AF 0.0529% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0515%

Overall 0.0431% 695/1,612,286 alleles · ultra-rare exomes 653/1,460,094 · genomes 42/152,192 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0565%	1,771
Remaining individualsnot grpmax-eligible	0.0192%	5,203
East Asian	0.00891%	11,218
African / African-American	0.00801%	12,487
Finnishnot grpmax-eligible	0.00633%	15,803
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,554
Admixed American	0.00167%	60,002
South Asian	0.0011%	91,010

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.Arg244His
Coding: c.731G>A
MANE Select: NM_000260
dbSNP: rs121965081
Type: single nucleotide variant
Location: chr11:77157000 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 244: the myosin motor domain; a UniProt-annotated variant site (in dfnb2)

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.Arg244Cys Likely pathogenic ★★ ⚠ same residue
MYO7A p.Arg244Pro Pathogenic ★ same residue
MYO7A p.Arg244Leu Uncertain significance ★ ⚠ 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

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-arg244his (accessed [today's date]).

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