Is MYO7B p.Phe1621Leu (c.4861T>C) pathogenic?

MYO7B p.Phe1621Leu (c.4861T>C) is classified Likely benign in MYO7B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely benign (0.1657); Ultra-rare (popmax 0.0825%, eas).

How common is MYO7B p.Phe1621Leu (c.4861T>C) in the general population?

MYO7B p.Phe1621Leu (c.4861T>C) is ultra-rare (popmax 0.0825%, eas) (gnomAD).

What do computational predictors say about MYO7B p.Phe1621Leu (c.4861T>C)?

AlphaMissense predicts likely benign (score 0.1657) — an in-silico prediction, not a clinical call.

MYO7B p.Phe1621Leu

c.4861T>C · rs549403034 · VCV3166362

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1657 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1657	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -3.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.069	GERP -2.5
Regional constraint	o/e 1.07	unconstrained · MANE · 7,741 bp · p 0.063 · regional, not allelic
Overall
CADD	0.937	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 F1595L vs ClinVar F1621L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0825% East Asian · 37/44,858 alleles

Filtering AF 0.0615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.00229% 37/1,612,782 alleles · ultra-rare exomes 32/1,460,666 · genomes 5/152,116 · joint denominator

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.Phe1621Leu
Coding: c.4861T>C
MANE Select: NM_001393586
dbSNP: rs549403034
Type: single nucleotide variant
Location: chr2:127630832 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 1595 UniProt numbering: 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.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-phe1621leu (accessed [today's date]).

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