Is CMAS p.Leu381Phe (c.1143G>T) pathogenic?

CMAS p.Leu381Phe (c.1143G>T) is classified Uncertain significance in CMAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-06). AlphaMissense: likely benign (0.327); Absent from gnomAD v4.1.

How common is CMAS p.Leu381Phe (c.1143G>T) in the general population?

CMAS p.Leu381Phe (c.1143G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CMAS p.Leu381Phe (c.1143G>T)?

AlphaMissense predicts likely benign (score 0.327) — an in-silico prediction, not a clinical call.

CMAS p.Leu381Phe

c.1143G>T · VCV3834279

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.327 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.327	likely benign
REVEL	0.247	benign-leaning
SaProt	LLR -11.61	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 3,912 bp · p 0.098 · regional, not allelic
Overall
CADD	23.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CMAS
Protein: p.Leu381Phe
Coding: c.1143G>T
MANE Select: NM_018686
Type: single nucleotide variant
Location: chr12:22065149 (GRCh38)
Gene constraint: LOEUF 0.566 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 88.10

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

Similar variants

CMAS p.Lys26= Benign ★★ same type
CMAS p.Tyr403= Benign/Likely benign ★★ same type
CMAS p.Ala328Pro Uncertain significance ★ ⚠ same type
CMAS p.Arg175Cys Uncertain significance ★ ⚠ same type
CMAS p.Arg175His Uncertain significance ★ ⚠ same type
CMAS p.Arg18Leu Uncertain significance ★ ⚠ same type
CMAS p.Arg203Cys Uncertain significance ★ ⚠ same type
CMAS p.Arg241Gln 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/cmas-p-leu381phe (accessed [today's date]).

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