Is MYO7B p.Ile1309Val (c.3925A>G) pathogenic?

MYO7B p.Ile1309Val (c.3925A>G) is classified Benign in MYO7B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2017-08-08). AlphaMissense: likely benign (0.105); Common (popmax 6.2%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about MYO7B p.Ile1309Val (c.3925A>G)?

AlphaMissense predicts likely benign (score 0.105) — an in-silico prediction, not a clinical call.

MYO7B p.Ile1309Val

Q: How common is MYO7B p.Ile1309Val (c.3925A>G) in the general population?

MYO7B p.Ile1309Val (c.3925A>G) is common (popmax 6.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3925A>G · rs116176015 · VCV775756

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.105 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.2%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.105	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -5.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5	GERP -3.2
Regional constraint	o/e 0.94	unconstrained · MANE · 69 kb · p 0.0075 · regional, not allelic
Overall
CADD	14.23	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 I1283V vs ClinVar I1309V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2% African / African-American · 4,628/74,612 alleles

Filtering AF 6.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.99%

Overall 0.334% 5,336/1,597,444 alleles · common exomes 2,681/1,445,124 · genomes 2,655/152,320 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.2%	16
Remaining individualsnot grpmax-eligible	0.388%	258
Admixed American	0.357%	280
Middle Eastern	0.215%	465
Ashkenazi Jewishnot grpmax-eligible	0.0617%	1,622
European (non-Finnish)	0.019%	5,259
South Asian	0.00569%	17,566
East Asian	0.00227%	44,028

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.Ile1309Val
Coding: c.3925A>G
MANE Select: NM_001393586
dbSNP: rs116176015
Type: single nucleotide variant
Location: chr2:127624198 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 1283 UniProt numbering: the 'mediates interaction with anks4b' 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.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
MYO7B p.Ala1154Val 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-ile1309val (accessed [today's date]).

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