Is MYO7B p.Ala1532Thr (c.4594G>A) pathogenic?

MYO7B p.Ala1532Thr (c.4594G>A) is classified Uncertain significance in MYO7B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-01). AlphaMissense: likely benign (0.0927); Ultra-rare (popmax 0.0201%, mid).

How common is MYO7B p.Ala1532Thr (c.4594G>A) in the general population?

MYO7B p.Ala1532Thr (c.4594G>A) is ultra-rare (popmax 0.0201%, mid) (gnomAD).

What do computational predictors say about MYO7B p.Ala1532Thr (c.4594G>A)?

AlphaMissense predicts likely benign (score 0.0927) — an in-silico prediction, not a clinical call.

MYO7B p.Ala1532Thr

c.4594G>A · rs1349444500 · VCV2354640

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0927 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0927	likely benign
REVEL	0.401	indeterminate
SaProt	LLR -10.77	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.4	GERP -2.4, phastCons 0.82
Regional constraint	o/e 0.94	unconstrained · MANE · 69 kb · p 0.0075 · regional, not allelic
Overall
CADD	19.2	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A1506T vs ClinVar A1532T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0201% Middle Eastern · 1/4,978 alleles

Filtering AF 0.00311% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00277%

Overall 0.00383% 56/1,462,570 alleles · ultra-rare exomes 54/1,332,946 · genomes 2/129,624 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0201%	4,978
Remaining individualsnot grpmax-eligible	0.00901%	11,101
European (non-Finnish)	0.00407%	24,542
Ashkenazi Jewishnot grpmax-eligible	0.0038%	26,340
African / African-American	0.00326%	30,721
East Asian	0.00269%	37,202
Admixed American	0.00224%	44,726

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.Ala1532Thr
Coding: c.4594G>A
MANE Select: NM_001393586
dbSNP: rs1349444500
Type: single nucleotide variant
Location: chr2:127628505 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 1506 UniProt numbering: the sh3 domain; the 'mediates interaction with anks4b' region; the 'mediates interaction with cdhr2, cdhr5 and ush1c' region; the ferm 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-ala1532thr (accessed [today's date]).

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