Is MYO7B p.Val1556Ile (c.4666G>A) pathogenic?

MYO7B p.Val1556Ile (c.4666G>A) is classified Benign in MYO7B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-31). AlphaMissense: likely benign (0.0636); Common (popmax 6.76%, amr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about MYO7B p.Val1556Ile (c.4666G>A)?

AlphaMissense predicts likely benign (score 0.0636) — an in-silico prediction, not a clinical call.

MYO7B p.Val1556Ile

Q: How common is MYO7B p.Val1556Ile (c.4666G>A) in the general population?

MYO7B p.Val1556Ile (c.4666G>A) is common (popmax 6.76%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4666G>A · rs61744676 · VCV770508

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0636 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.76%, amr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0636	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -6.22	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 2.5	GERP -1.6, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 7,741 bp · p 0.063 · regional, not allelic
Overall
CADD	7.302	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 V1530I vs ClinVar V1556I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.76% Admixed American · 4,050/59,904 alleles

Filtering AF 6.59% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.52%

Overall 0.324% 5,220/1,612,398 alleles · common exomes 4,341/1,460,038 · genomes 879/152,360 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	6.76%	15
East Asian	1.46%	68
Remaining individualsnot grpmax-eligible	0.34%	294
African / African-American	0.101%	987
South Asian	0.0967%	1,034
Ashkenazi Jewishnot grpmax-eligible	0.0237%	4,225
Middle Eastern	0.0165%	6,056
European (non-Finnish)	0.0112%	8,935

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.Val1556Ile
Coding: c.4666G>A
MANE Select: NM_001393586
dbSNP: rs61744676
Type: single nucleotide variant
Location: chr2:127629686 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 1530 UniProt numbering: the sh3 domain; the 'mediates interaction with anks4b' region; the 'mediates interaction with cdhr2, cdhr5 and ush1c' region

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.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-val1556ile (accessed [today's date]).

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