Is CIPC p.Pro381Ser (c.1141C>T) pathogenic?

CIPC p.Pro381Ser (c.1141C>T) is classified Likely benign in CIPC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). AlphaMissense: likely benign (0.0581); Very rare (popmax 0.0011%, sas).

How common is CIPC p.Pro381Ser (c.1141C>T) in the general population?

CIPC p.Pro381Ser (c.1141C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CIPC p.Pro381Ser (c.1141C>T)?

AlphaMissense predicts likely benign (score 0.0581) — an in-silico prediction, not a clinical call.

CIPC p.Pro381Ser

c.1141C>T · VCV4003121

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0581 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0581	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -12.27	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1	GERP -3.5
Regional constraint	o/e 0.86	unconstrained · MANE · 8,606 bp · p 0.0016 · regional, not allelic
Overall
CADD	1.804	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 0.0011% South Asian · 1/91,072 alleles

Overall 0.000124% 2/1,613,872 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,072
European (non-Finnish)	8.47e-05%	1,179,994

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.Pro381Ser
Coding: c.1141C>T
MANE Select: NM_033426
Type: single nucleotide variant
Location: chr14:77114259 (GRCh38)
Gene constraint: LOEUF 0.64 · pLI 0.44 (gnomAD)
Structure: AlphaFold pLDDT 58.88
Residue 381: the 'disordered' region

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

Similar variants

CIPC p.Pro381Ala Uncertain significance ★ ⚠ same residue
CIPC p.Pro381Arg Uncertain significance ★ ⚠ same residue
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

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-pro381ser (accessed [today's date]).

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