Is CMAS p.Arg18Leu (c.53G>T) pathogenic?

CMAS p.Arg18Leu (c.53G>T) is classified Uncertain significance in CMAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.1296); Absent from gnomAD v4.1.

How common is CMAS p.Arg18Leu (c.53G>T) in the general population?

CMAS p.Arg18Leu (c.53G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CMAS p.Arg18Leu (c.53G>T)?

AlphaMissense predicts likely benign (score 0.1296) — an in-silico prediction, not a clinical call.

CMAS p.Arg18Leu

c.53G>T · rs2542046949 · VCV3146200

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1296 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,530,134)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1296	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -8.21	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 11	GERP 0.93, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 8,876 bp · p 0.065 · regional, not allelic
Overall
CADD	24.0	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

No allele count reported in gnomAD v4.1 (AN 1,530,134). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CMAS
Protein: p.Arg18Leu
Coding: c.53G>T
MANE Select: NM_018686
dbSNP: rs2542046949
Type: single nucleotide variant
Location: chr12:22046356 (GRCh38)
Gene constraint: LOEUF 0.566 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 88.10
Residue 18: the 'disordered' region

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.Arg203Cys Uncertain significance ★ ⚠ same type
CMAS p.Arg241Gln 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-arg18leu (accessed [today's date]).

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