Is CMAS p.Arg241Gln (c.722G>A) pathogenic?

CMAS p.Arg241Gln (c.722G>A) is classified Uncertain significance in CMAS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-24). AlphaMissense: likely benign (0.0961); Ultra-rare (popmax 0.0209%, sas).

How common is CMAS p.Arg241Gln (c.722G>A) in the general population?

CMAS p.Arg241Gln (c.722G>A) is ultra-rare (popmax 0.0209%, sas) (gnomAD).

What do computational predictors say about CMAS p.Arg241Gln (c.722G>A)?

AlphaMissense predicts likely benign (score 0.0961) — an in-silico prediction, not a clinical call.

CMAS p.Arg241Gln

c.722G>A · rs767789328 · VCV3146202

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0961 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0961	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -4.39	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 6.6	GERP 0.36, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 6,214 bp · p 4.4e-12 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0209% South Asian · 19/90,952 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.00248% 40/1,611,332 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0209%	4,787
African / African-American	0.00935%	10,690
East Asian	0.00671%	14,911
Admixed American	0.00333%	29,989
European (non-Finnish)	0.000764%	130,883

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.Arg241Gln
Coding: c.722G>A
MANE Select: NM_018686
dbSNP: rs767789328
Type: single nucleotide variant
Location: chr12:22060860 (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.Arg415Gln 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-arg241gln (accessed [today's date]).

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