Is MYO7B p.Glu970Lys (c.2908G>A) pathogenic?

MYO7B p.Glu970Lys (c.2908G>A) is classified Uncertain significance in MYO7B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-08). AlphaMissense: likely benign (0.1118); Ultra-rare (popmax 0.025%, amr).

How common is MYO7B p.Glu970Lys (c.2908G>A) in the general population?

MYO7B p.Glu970Lys (c.2908G>A) is ultra-rare (popmax 0.025%, amr) (gnomAD).

What do computational predictors say about MYO7B p.Glu970Lys (c.2908G>A)?

AlphaMissense predicts likely benign (score 0.1118) — an in-silico prediction, not a clinical call.

MYO7B p.Glu970Lys

c.2908G>A · rs775462069 · VCV3166239

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1118 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1118	likely benign
REVEL	0.499	indeterminate
SaProt	LLR -6.63	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.28	donor gain · deltas
Constraint at this position
Conservation	phyloP 1.9	GERP 0.62, phastCons 0.85
Regional constraint	o/e 0.94	unconstrained · MANE · 69 kb · p 0.0075 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.025% Admixed American · 15/60,002 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.00105% 17/1,613,900 alleles · ultra-rare exomes 13/1,461,704 · genomes 4/152,196 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.025%	4,000
European (non-Finnish)	0.00017%	589,950

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.Glu970Lys
Coding: c.2908G>A
MANE Select: NM_001393586
dbSNP: rs775462069
Type: single nucleotide variant
Location: chr2:127609599 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 970: the 'mediates interaction with anks4b' region

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

Similar variants

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MYO7B p.Val1556Ile Benign ★★ same type
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
MYO7B p.Ala1126Thr Uncertain significance ★ ⚠ 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/myo7b-p-glu970lys (accessed [today's date]).

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