Is MYO7A p.Arg866Cys (c.2596C>T) pathogenic?

MYO7A p.Arg866Cys (c.2596C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-07). AlphaMissense: ambiguous (0.3463); Ultra-rare (popmax 0.0165%, mid).

How common is MYO7A p.Arg866Cys (c.2596C>T) in the general population?

MYO7A p.Arg866Cys (c.2596C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about MYO7A p.Arg866Cys (c.2596C>T)?

AlphaMissense predicts ambiguous (score 0.3463) — an in-silico prediction, not a clinical call.

MYO7A p.Arg866Cys

c.2596C>T · rs782487264 · VCV2150573

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3463 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Computational evidence

Protein change
AlphaMissense	0.3463	ambiguous
REVEL	0.629	indeterminate
SaProt	LLR -11.33	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 0.56, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	25.2	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 0.0165% Middle Eastern · 1/6,078 alleles

Filtering AF 0.00307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00354% 57/1,612,044 alleles · ultra-rare exomes 51/1,459,892 · genomes 6/152,152 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,078
African / African-American	0.00534%	18,730
European (non-Finnish)	0.00398%	25,097
Finnishnot grpmax-eligible	0.00318%	31,484
Admixed American	0.00167%	59,904
Remaining individualsnot grpmax-eligible	0.0016%	62,426
South Asian	0.0011%	90,806

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.Arg866Cys
Coding: c.2596C>T
MANE Select: NM_000260
dbSNP: rs782487264
Type: single nucleotide variant
Location: chr11:77180383 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 866: the 'sah' region

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

Similar variants

MYO7A p.Arg866His Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg866= Conflicting classifications of pathogenicity ★ same residue
MYO7A p.Arg866Pro Uncertain significance ★ ⚠ same residue
MYO7A p.Arg866Ser 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

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-arg866cys (accessed [today's date]).

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