Is MYO7B p.Leu2097Arg (c.6290T>G) pathogenic?

MYO7B p.Leu2097Arg (c.6290T>G) is classified Uncertain significance in MYO7B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-10). AlphaMissense: likely benign (0.2097); Very rare (popmax 0.00267%, afr).

How common is MYO7B p.Leu2097Arg (c.6290T>G) in the general population?

MYO7B p.Leu2097Arg (c.6290T>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about MYO7B p.Leu2097Arg (c.6290T>G)?

AlphaMissense predicts likely benign (score 0.2097) — an in-silico prediction, not a clinical call.

MYO7B p.Leu2097Arg

c.6290T>G · rs751352376 · VCV2328633

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2097 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2097	likely benign
REVEL	0.871	moderately pathogenic-leaning
SaProt	LLR -6.12	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.1	GERP 1.9, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 7,741 bp · p 0.063 · regional, not allelic
Overall
CADD	25.3	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 L2071R vs ClinVar L2097R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,788 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00149% 24/1,612,694 alleles · very rare exomes 20/1,460,980 · genomes 4/151,714 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,394
European (non-Finnish)	0.00187%	53,616

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.Leu2097Arg
Coding: c.6290T>G
MANE Select: NM_001393586
dbSNP: rs751352376
Type: single nucleotide variant
Location: chr2:127636876 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 2071 UniProt numbering: the ferm 2 domain; the 'mediates interaction with cdhr2, cdhr5 and ush1c' region

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

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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-leu2097arg (accessed [today's date]).

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