Is CSH1 p.Arg204Ser (c.610C>A) pathogenic?

CSH1 p.Arg204Ser (c.610C>A) is classified Uncertain significance in CSH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-10). AlphaMissense: ambiguous (0.4812); Ultra-rare (popmax 0.0111%, eas).

How common is CSH1 p.Arg204Ser (c.610C>A) in the general population?

CSH1 p.Arg204Ser (c.610C>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about CSH1 p.Arg204Ser (c.610C>A)?

AlphaMissense predicts ambiguous (score 0.4812) — an in-silico prediction, not a clinical call.

CSH1 p.Arg204Ser

c.610C>A · rs139446025 · VCV3078033

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4812 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Computational evidence

Protein change
AlphaMissense	0.4812	ambiguous
REVEL	0.623	indeterminate
SaProt	LLR -8.25	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.63, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 1,060 bp · p 0.37 · regional, not allelic
Overall
CADD	21.0	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

Grpmax group 0.0111% East Asian · 5/44,872 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00031% 5/1,612,988 alleles · ultra-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: CSH1
Protein: p.Arg204Ser
Coding: c.610C>A
MANE Select: NM_001317
dbSNP: rs139446025
Type: single nucleotide variant
Location: chr17:63895066 (GRCh38)
Gene constraint: LOEUF 1.213 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.67 · 1 PDB
Residue 204: an α-helix

Full CSH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSH1 p.Ala14Gly Uncertain significance ★ ⚠ same type
CSH1 p.Ala2Thr Uncertain significance ★ ⚠ same type
CSH1 p.Arg159His Uncertain significance ★ ⚠ same type
CSH1 p.Arg160Trp Uncertain significance ★ ⚠ same type
CSH1 p.Arg6Gln Uncertain significance ★ ⚠ same type
CSH1 p.Asp135Asn Uncertain significance ★ ⚠ same type
CSH1 p.Asp180His Uncertain significance ★ ⚠ same type
CSH1 p.Asp37Glu 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/csh1-p-arg204ser (accessed [today's date]).

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