Is CMSS1 p.Arg204Ser (c.610C>A) pathogenic?

CMSS1 p.Arg204Ser (c.610C>A) is classified Uncertain significance in CMSS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-03). AlphaMissense: likely benign (0.1674); Absent from gnomAD v4.1.

How common is CMSS1 p.Arg204Ser (c.610C>A) in the general population?

CMSS1 p.Arg204Ser (c.610C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CMSS1 p.Arg204Ser (c.610C>A)?

AlphaMissense predicts likely benign (score 0.1674) — an in-silico prediction, not a clinical call.

CMSS1 p.Arg204Ser

c.610C>A · VCV3494142

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1674 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1674	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -4.71	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 2.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 360 kb · p 0.46 · regional, not allelic
Overall
CADD	21.1	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

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: CMSS1
Protein: p.Arg204Ser
Coding: c.610C>A
MANE Select: NM_032359
Type: single nucleotide variant
Location: chr3:100172346 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.31

Full CMSS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CMSS1 p.Arg204Cys Uncertain significance ★ ⚠ same residue
CMSS1 p.Ala83Gly Uncertain significance ★ ⚠ same type
CMSS1 p.Arg107Cys Uncertain significance ★ ⚠ same type
CMSS1 p.Arg107His Uncertain significance ★ ⚠ same type
CMSS1 p.Asp94Gly Uncertain significance ★ ⚠ same type
CMSS1 p.Cys121Arg Uncertain significance ★ ⚠ same type
CMSS1 p.Glu138Gln Uncertain significance ★ ⚠ same type
CMSS1 p.Glu218Asp 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/cmss1-p-arg204ser (accessed [today's date]).

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