Is CIPC p.Pro292Ala (c.874C>G) pathogenic?

CIPC p.Pro292Ala (c.874C>G) is classified Uncertain significance in CIPC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-25). AlphaMissense: likely benign (0.0707); Rare (popmax 0.297%, mid).

How common is CIPC p.Pro292Ala (c.874C>G) in the general population?

CIPC p.Pro292Ala (c.874C>G) is rare (popmax 0.297%, mid) (gnomAD).

What do computational predictors say about CIPC p.Pro292Ala (c.874C>G)?

AlphaMissense predicts likely benign (score 0.0707) — an in-silico prediction, not a clinical call.

CIPC p.Pro292Ala

c.874C>G · rs200854666 · VCV3145115

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0707 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.297%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0707	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -7.20	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 1.9	GERP -1.6, phastCons 0.94
Regional constraint	o/e 0.86	unconstrained · MANE · 8,606 bp · p 0.0016 · regional, not allelic
Overall
CADD	14.69	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

Grpmax group 0.297% Middle Eastern · 18/6,062 alleles

Filtering AF 0.192% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.159%

Overall 0.0151% 243/1,614,248 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.297%	337
Ashkenazi Jewishnot grpmax-eligible	0.0676%	1,480
Admixed American	0.0466%	2,144
Remaining individualsnot grpmax-eligible	0.0432%	2,315
African / African-American	0.0253%	3,951
European (non-Finnish)	0.0108%	9,292
South Asian	0.00439%	22,771

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: CIPC
Protein: p.Pro292Ala
Coding: c.874C>G
MANE Select: NM_033426
dbSNP: rs200854666
Type: single nucleotide variant
Location: chr14:77113992 (GRCh38)
Gene constraint: LOEUF 0.64 · pLI 0.44 (gnomAD)
Structure: AlphaFold pLDDT 58.88

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

Similar variants

CIPC p.Ala220Thr Uncertain significance ★ ⚠ same type
CIPC p.Ala373Ser Uncertain significance ★ ⚠ same type
CIPC p.Arg29His Uncertain significance ★ ⚠ same type
CIPC p.Arg301Cys Uncertain significance ★ ⚠ same type
CIPC p.Arg301His Uncertain significance ★ ⚠ same type
CIPC p.Arg310Gln Uncertain significance ★ ⚠ same type
CIPC p.Arg310Trp Uncertain significance ★ ⚠ same type
CIPC p.Asn288His 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/cipc-p-pro292ala (accessed [today's date]).

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