Is MYO7B p.Leu839= (c.2517G>A) pathogenic?

MYO7B p.Leu839= (c.2517G>A) is classified Likely benign in MYO7B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-17). Rare (popmax 0.199%, afr); Associated with MYO7B-related disorder.

What condition is associated with MYO7B p.Leu839= (c.2517G>A)?

MYO7B p.Leu839= (c.2517G>A) is associated with MYO7B-related disorder (ClinVar).

How common is MYO7B p.Leu839= (c.2517G>A) in the general population?

MYO7B p.Leu839= (c.2517G>A) is rare (popmax 0.199%, afr) (gnomAD).

MYO7B p.Leu839=

c.2517G>A · rs199821381 · VCV3034262

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.199%, afr)

Conditions

MYO7B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.51	GERP -0.34, phastCons 0.99
Overall
CADD	6.855	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.199% African / African-American · 146/73,200 alleles

Filtering AF 0.173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.163%

Overall 0.011% 171/1,551,388 alleles · rare exomes 81/1,398,994 · genomes 90/152,394 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.199%	501
Admixed American	0.0235%	4,252
Middle Eastern	0.0168%	5,970
Remaining individualsnot grpmax-eligible	0.0166%	6,010
European (non-Finnish)	0.000174%	573,480

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.Leu839=
Coding: c.2517G>A
MANE Select: NM_001393586
dbSNP: rs199821381
Type: single nucleotide variant
Location: chr2:127607298 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 839: the iq 5 domain

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

Disease context

MYO7B-related disorder

Similar variants

MYO7B p.Ala397Ser Uncertain significance ⚠ same condition
MYO7B c.1081-10G>T Benign same condition
MYO7B c.1691-7T>C Benign same condition
MYO7B c.2339+4C>T Benign same condition
MYO7B c.4333+8C>A Likely benign same condition
MYO7B c.5714-7C>T Benign same condition
MYO7B c.5821-8T>C Benign same condition
MYO7B c.6123+9T>C Benign same condition

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-leu839 (accessed [today's date]).

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