Is CHIC1 p.Pro111Ser (c.331C>T) pathogenic?

CHIC1 p.Pro111Ser (c.331C>T) is classified Uncertain significance in CHIC1 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.9845); Absent from gnomAD v4.1; Associated with prostate cancer.

What condition is associated with CHIC1 p.Pro111Ser (c.331C>T)?

CHIC1 p.Pro111Ser (c.331C>T) is associated with prostate cancer (ClinVar).

How common is CHIC1 p.Pro111Ser (c.331C>T) in the general population?

CHIC1 p.Pro111Ser (c.331C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHIC1 p.Pro111Ser (c.331C>T)?

AlphaMissense predicts likely pathogenic (score 0.9845) — an in-silico prediction, not a clinical call.

CHIC1 p.Pro111Ser

c.331C>T · rs864622038 · VCV219349

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9845 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

prostate cancer

Computational evidence

Protein change
AlphaMissense	0.9845	likely pathogenic
REVEL	0.941	strongly pathogenic-leaning
SaProt	LLR -12.74	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 118 kb · p 0.18 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: CHIC1
Protein: p.Pro111Ser
Coding: c.331C>T
MANE Select: NM_001039840
dbSNP: rs864622038
Type: single nucleotide variant
Location: chrX:73577441 (GRCh38)
Structure: AlphaFold pLDDT 74.69

Full CHIC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

prostate cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHIC1 p.Arg222Gln Uncertain significance ★ ⚠ same type
CHIC1 p.Arg74Trp Uncertain significance ★ ⚠ same type
CHIC1 p.Asn204Thr Uncertain significance ★ same type
CHIC1 p.Asp44Asn Uncertain significance ★ ⚠ same type
CHIC1 p.Cys133Ser Uncertain significance ★ same type
CHIC1 p.Glu24Ala Uncertain significance ★ ⚠ same type
CHIC1 p.Glu45Lys Uncertain significance ★ ⚠ same type
CHIC1 p.Glu50Gly 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/chic1-p-pro111ser (accessed [today's date]).

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