Is MYO7B p.Lys542Gln (c.1624A>C) pathogenic?

MYO7B p.Lys542Gln (c.1624A>C) is classified Uncertain significance in MYO7B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-22). AlphaMissense: likely benign (0.1051); Rare (popmax 0.133%, afr).

How common is MYO7B p.Lys542Gln (c.1624A>C) in the general population?

MYO7B p.Lys542Gln (c.1624A>C) is rare (popmax 0.133%, afr) (gnomAD).

What do computational predictors say about MYO7B p.Lys542Gln (c.1624A>C)?

AlphaMissense predicts likely benign (score 0.1051) — an in-silico prediction, not a clinical call.

MYO7B p.Lys542Gln

c.1624A>C · rs369143572 · VCV2390010

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1051 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1051	likely benign
REVEL	0.512	indeterminate
SaProt	LLR -10.13	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 6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 69 kb · p 0.0075 · regional, not allelic
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.133% African / African-American · 100/75,040 alleles

Filtering AF 0.112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.104%

Overall 0.00762% 123/1,613,982 alleles · rare exomes 79/1,461,710 · genomes 44/152,272 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.133%	750
Remaining individualsnot grpmax-eligible	0.0176%	5,681
Middle Eastern	0.0165%	6,062
Admixed American	0.0133%	7,501
South Asian	0.00329%	30,361

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.Lys542Gln
Coding: c.1624A>C
MANE Select: NM_001393586
dbSNP: rs369143572
Type: single nucleotide variant
Location: chr2:127584847 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 542: the myosin motor 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-lys542gln (accessed [today's date]).

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