Is CMAS p.Ala389Val (c.1166C>T) pathogenic?

CMAS p.Ala389Val (c.1166C>T) is classified Likely benign in CMAS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: likely benign (0.0652); Very rare (popmax 0.005%, amr).

How common is CMAS p.Ala389Val (c.1166C>T) in the general population?

CMAS p.Ala389Val (c.1166C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about CMAS p.Ala389Val (c.1166C>T)?

AlphaMissense predicts likely benign (score 0.0652) — an in-silico prediction, not a clinical call.

CMAS p.Ala389Val

c.1166C>T · rs1019693008 · VCV2547493

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0652 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0652	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -7.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.85, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 3,912 bp · p 0.098 · regional, not allelic
Overall
CADD	14.41	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 0.005% Admixed American · 3/60,016 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000205% 3/1,461,664 alleles · very rare

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: CMAS
Protein: p.Ala389Val
Coding: c.1166C>T
MANE Select: NM_018686
dbSNP: rs1019693008
Type: single nucleotide variant
Location: chr12:22065172 (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-ala389val (accessed [today's date]).

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