Is CLIC3 p.Arg204Ser (c.610C>A) pathogenic?

CLIC3 p.Arg204Ser (c.610C>A) is classified Uncertain significance in CLIC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). AlphaMissense: likely benign (0.3074); Very rare (popmax 0.00173%, amr).

How common is CLIC3 p.Arg204Ser (c.610C>A) in the general population?

CLIC3 p.Arg204Ser (c.610C>A) is very rare (popmax 0.00173%, amr) (gnomAD).

What do computational predictors say about CLIC3 p.Arg204Ser (c.610C>A)?

AlphaMissense predicts likely benign (score 0.3074) — an in-silico prediction, not a clinical call.

CLIC3 p.Arg204Ser

c.610C>A · rs900063658 · VCV3145761

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3074 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00173%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3074	likely benign
REVEL	0.368	indeterminate
SaProt	LLR -11.45	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -1.3, phastCons 0.005
Regional constraint	o/e 1.07	unconstrained · MANE · 1,859 bp · p 0.23 · regional, not allelic
Overall
CADD	19.87	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 0.00173% Admixed American · 1/57,888 alleles

Overall 0.000208% 3/1,443,942 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00173%	57,888
Finnishnot grpmax-eligible	0.00163%	61,192
European (non-Finnish)	8.53e-05%	1,172,196

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: CLIC3
Protein: p.Arg204Ser
Coding: c.610C>A
MANE Select: NM_004669
dbSNP: rs900063658
Type: single nucleotide variant
Location: chr9:136994782 (GRCh38)
Gene constraint: LOEUF 1.903 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.08 · 2 PDB
Residue 204: an α-helix; the gst c-terminal domain

Full CLIC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLIC3 p.Ala151Val Uncertain significance ★ ⚠ same type
CLIC3 p.Ala188Thr Uncertain significance ★ ⚠ same type
CLIC3 p.Ala209Thr Uncertain significance ★ ⚠ same type
CLIC3 p.Ala2Val Uncertain significance ★ ⚠ same type
CLIC3 p.Arg191Cys Uncertain significance ★ ⚠ same type
CLIC3 p.Arg200His Uncertain significance ★ ⚠ same type
CLIC3 p.Arg27Gln Uncertain significance ★ ⚠ same type
CLIC3 p.Cys22Tyr 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/clic3-p-arg204ser (accessed [today's date]).

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