Is MYO7B p.Glu1002Lys (c.3004G>A) pathogenic?

MYO7B p.Glu1002Lys (c.3004G>A) is classified Uncertain significance in MYO7B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-28). AlphaMissense: likely benign (0.1107); Ultra-rare (popmax 0.0802%, sas).

How common is MYO7B p.Glu1002Lys (c.3004G>A) in the general population?

MYO7B p.Glu1002Lys (c.3004G>A) is ultra-rare (popmax 0.0802%, sas) (gnomAD).

What do computational predictors say about MYO7B p.Glu1002Lys (c.3004G>A)?

AlphaMissense predicts likely benign (score 0.1107) — an in-silico prediction, not a clinical call.

MYO7B p.Glu1002Lys

c.3004G>A · rs574346274 · VCV3166249

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1107 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0802%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1107	likely benign
REVEL	0.501	indeterminate
SaProt	LLR -5.14	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 69 kb · p 0.0075 · regional, not allelic
Overall
CADD	23.5	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 0.0802% South Asian · 73/91,072 alleles

Filtering AF 0.0654% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0599%

Overall 0.00576% 93/1,613,940 alleles · ultra-rare exomes 90/1,461,696 · genomes 3/152,244 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0802%	1,248
Middle Eastern	0.0165%	6,062
African / African-American	0.004%	25,009
Remaining individualsnot grpmax-eligible	0.0032%	31,243
East Asian	0.00223%	44,876
Admixed American	0.00167%	60,024
European (non-Finnish)	0.00102%	98,323

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.Glu1002Lys
Coding: c.3004G>A
MANE Select: NM_001393586
dbSNP: rs574346274
Type: single nucleotide variant
Location: chr2:127609695 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 1002: the 'mediates interaction with anks4b' region; the myth4 1 domain

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

Similar variants

MYO7B p.Thr349Met Uncertain significance ★★ ⚠ same type
MYO7B p.Ile1309Val Benign ★★ same type
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-glu1002lys (accessed [today's date]).

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