Is CHIC1 p.Ser77Arg (c.231C>G) pathogenic?

CHIC1 p.Ser77Arg (c.231C>G) is classified Uncertain significance in CHIC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-21). AlphaMissense: likely pathogenic (0.7511); Absent from gnomAD v4.1.

How common is CHIC1 p.Ser77Arg (c.231C>G) in the general population?

CHIC1 p.Ser77Arg (c.231C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHIC1 p.Ser77Arg (c.231C>G)?

AlphaMissense predicts likely pathogenic (score 0.7511) — an in-silico prediction, not a clinical call.

CHIC1 p.Ser77Arg

c.231C>G · rs2519718996 · VCV2527391

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7511 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7511	likely pathogenic
REVEL	0.133	moderately benign-leaning
SaProt	LLR -7.00	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.55 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.54	GERP 0.89, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 118 kb · p 0.18 · regional, not allelic
Overall
CADD	22.8	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

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.Ser77Arg
Coding: c.231C>G
MANE Select: NM_001039840
dbSNP: rs2519718996
Type: single nucleotide variant
Location: chrX:73563515 (GRCh38)
Structure: AlphaFold pLDDT 74.69
Residue 77: the 'disordered' region

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

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-ser77arg (accessed [today's date]).

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