Is MYO7A p.Arg825Cys (c.2473C>T) pathogenic?

MYO7A p.Arg825Cys (c.2473C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-13). AlphaMissense: likely pathogenic (0.6766); Very rare (popmax 0.00392%, amr).

How common is MYO7A p.Arg825Cys (c.2473C>T) in the general population?

MYO7A p.Arg825Cys (c.2473C>T) is very rare (popmax 0.00392%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Arg825Cys (c.2473C>T)?

AlphaMissense predicts likely pathogenic (score 0.6766) — an in-silico prediction, not a clinical call.

MYO7A p.Arg825Cys

c.2473C>T · rs1394439593 · VCV970504

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6766 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00392%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6766	likely pathogenic
REVEL	0.817	moderately pathogenic-leaning
SaProt	LLR -12.89	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 2.1	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00392% Admixed American · 2/51,048 alleles

Filtering AF 0.00158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.0022% 34/1,543,080 alleles · very rare exomes 28/1,390,802 · genomes 6/152,278 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00392%	25,524
Remaining individualsnot grpmax-eligible	0.00333%	29,993
African / African-American	0.00274%	36,530
East Asian	0.00244%	40,956
European (non-Finnish)	0.00227%	44,115
South Asian	0.00119%	84,032

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.Arg825Cys
Coding: c.2473C>T
MANE Select: NM_000260
dbSNP: rs1394439593
Type: single nucleotide variant
Location: chr11:77179840 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 825: the iq 4 domain

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

Similar variants

MYO7A p.Arg825His Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg825= Conflicting classifications of pathogenicity ★ same residue
MYO7A p.Arg825Gly Uncertain significance ★ ⚠ 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-arg825cys (accessed [today's date]).

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