Is MYO7A p.Pro1556Leu (c.4667C>T) pathogenic?

MYO7A p.Pro1556Leu (c.4667C>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-05-13). AlphaMissense: likely benign (0.0952); Rare (popmax 0.184%, afr).

How common is MYO7A p.Pro1556Leu (c.4667C>T) in the general population?

MYO7A p.Pro1556Leu (c.4667C>T) is rare (popmax 0.184%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Pro1556Leu (c.4667C>T)?

AlphaMissense predicts likely benign (score 0.0952) — an in-silico prediction, not a clinical call.

MYO7A p.Pro1556Leu

c.4667C>T · rs150654627 · VCV218435

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0952 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.184%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0952	likely benign
REVEL	0.201	benign-leaning
SaProt	LLR -6.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.58 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	20.9	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 0.184% African / African-American · 138/75,006 alleles

Filtering AF 0.159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.15%

Overall 0.0128% 206/1,610,450 alleles · rare exomes 124/1,458,128 · genomes 82/152,322 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.184%	544
Remaining individualsnot grpmax-eligible	0.0208%	4,797
Admixed American	0.0201%	4,972
Middle Eastern	0.0165%	6,044
Finnishnot grpmax-eligible	0.00634%	15,778
South Asian	0.00332%	30,081
European (non-Finnish)	0.00297%	33,682

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: MYO7A
Protein: p.Pro1556Leu
Coding: c.4667C>T
MANE Select: NM_000260
dbSNP: rs150654627
Type: single nucleotide variant
Location: chr11:77199633 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1556: the ferm 1 domain

Full MYO7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MYO7A p.Pro1556= Benign/Likely benign ★★ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same type
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same type
MYO7A p.Arg668Cys Pathogenic ★★★ same type
MYO7A p.Arg853His Likely pathogenic ★★★ same type
MYO7A p.Glu968Asp Likely pathogenic ★★★ ⚠ 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/myo7a-p-pro1556leu (accessed [today's date]).

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