Is MYO7B p.Ala766Val (c.2297C>T) pathogenic?

MYO7B p.Ala766Val (c.2297C>T) is classified Uncertain significance in MYO7B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-25). AlphaMissense: likely benign (0.1229); Ultra-rare (popmax 0.0161%, nfe).

How common is MYO7B p.Ala766Val (c.2297C>T) in the general population?

MYO7B p.Ala766Val (c.2297C>T) is ultra-rare (popmax 0.0161%, nfe) (gnomAD).

What do computational predictors say about MYO7B p.Ala766Val (c.2297C>T)?

AlphaMissense predicts likely benign (score 0.1229) — an in-silico prediction, not a clinical call.

MYO7B p.Ala766Val

c.2297C>T · rs199683153 · VCV3166195

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1229 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0161%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1229	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -12.18	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.4	GERP -0.18, phastCons 0.56
Regional constraint	o/e 0.94	unconstrained · MANE · 69 kb · p 0.0075 · regional, not allelic
Overall
CADD	22.2	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 0.0161% European (non-Finnish) · 190/1,179,758 alleles

Filtering AF 0.0142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0134%

Overall 0.0141% 227/1,613,476 alleles · ultra-rare exomes 211/1,461,310 · genomes 16/152,166 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0312%	3,201
European (non-Finnish)grpmax	0.0161%	6,209
Remaining individualsnot grpmax-eligible	0.0128%	7,805
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,793
South Asian	0.0055%	18,188
Admixed American	0.00167%	59,954
African / African-American	0.00133%	74,914

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: MYO7B
Protein: p.Ala766Val
Coding: c.2297C>T
MANE Select: NM_001393586
dbSNP: rs199683153
Type: single nucleotide variant
Location: chr2:127596514 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 766: the iq 2 domain

Full MYO7B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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MYO7B p.Val1876= Benign ★★ same type
MYO7B p.Ala1010Thr Uncertain significance ★ ⚠ same type
MYO7B p.Ala1092Thr Uncertain significance ★ ⚠ same type
MYO7B p.Ala1109Thr Uncertain significance ★ ⚠ same type
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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/myo7b-p-ala766val (accessed [today's date]).

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