Is MYO7A p.Arg802His (c.2405G>A) pathogenic?

MYO7A p.Arg802His (c.2405G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-18). AlphaMissense: likely benign (0.27); Ultra-rare (popmax 0.0825%, eas).

How common is MYO7A p.Arg802His (c.2405G>A) in the general population?

MYO7A p.Arg802His (c.2405G>A) is ultra-rare (popmax 0.0825%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Arg802His (c.2405G>A)?

AlphaMissense predicts likely benign (score 0.27) — an in-silico prediction, not a clinical call.

MYO7A p.Arg802His

c.2405G>A · rs542110883 · VCV2066931

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.27 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.27	likely benign
REVEL	0.795	moderately pathogenic-leaning
SaProt	LLR -5.37	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 0.56, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	22.8	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 0.0825% East Asian · 34/41,214 alleles

Filtering AF 0.0606% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0531%

Overall 0.00509% 79/1,550,600 alleles · ultra-rare exomes 68/1,398,266 · genomes 11/152,334 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0825%	1,212
Admixed American	0.0135%	7,426
Remaining individualsnot grpmax-eligible	0.00499%	20,057
African / African-American	0.00409%	24,457
European (non-Finnish)	0.0027%	37,083
South Asian	0.00119%	84,334

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.Arg802His
Coding: c.2405G>A
MANE Select: NM_000260
dbSNP: rs542110883
Type: single nucleotide variant
Location: chr11:77179772 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 802: the iq 3 domain

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

Similar variants

MYO7A p.Arg802Cys Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg802Gly Uncertain significance ★ ⚠ same residue
MYO7A p.Arg802= Likely benign ★ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same type
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same type
MYO7A p.Arg668Cys Pathogenic ★★★ same type

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-arg802his (accessed [today's date]).

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