Is MYO7B p.Leu1160Phe (c.3478C>T) pathogenic?

MYO7B p.Leu1160Phe (c.3478C>T) is classified Uncertain significance in MYO7B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-08). AlphaMissense: ambiguous (0.3742); Ultra-rare (popmax 0.0267%, afr).

How common is MYO7B p.Leu1160Phe (c.3478C>T) in the general population?

MYO7B p.Leu1160Phe (c.3478C>T) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

What do computational predictors say about MYO7B p.Leu1160Phe (c.3478C>T)?

AlphaMissense predicts ambiguous (score 0.3742) — an in-silico prediction, not a clinical call.

MYO7B p.Leu1160Phe

c.3478C>T · VCV3876988

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3742 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3742	ambiguous
REVEL	0.808	moderately pathogenic-leaning
SaProt	LLR -10.09	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.8	GERP -3.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 69 kb · p 0.0075 · regional, not allelic
Overall
CADD	25.5	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 L1134F vs ClinVar L1160F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% African / African-American · 20/74,862 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.0013% 21/1,610,470 alleles · ultra-rare exomes 8/1,458,406 · genomes 13/152,064 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0267%	3,743
European (non-Finnish)	8.49e-05%	1,177,442

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.Leu1160Phe
Coding: c.3478C>T
MANE Select: NM_001393586
Type: single nucleotide variant
Location: chr2:127620419 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 1134 UniProt numbering: the 'mediates interaction with anks4b' region; the myth4 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.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-leu1160phe (accessed [today's date]).

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