Is CIPC p.Val120Leu (c.358G>T) pathogenic?

CIPC p.Val120Leu (c.358G>T) is classified Uncertain significance in CIPC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely pathogenic (0.5974); Absent from gnomAD v4.1.

How common is CIPC p.Val120Leu (c.358G>T) in the general population?

CIPC p.Val120Leu (c.358G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CIPC p.Val120Leu (c.358G>T)?

AlphaMissense predicts likely pathogenic (score 0.5974) — an in-silico prediction, not a clinical call.

CIPC p.Val120Leu

c.358G>T · VCV4653931

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5974 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5974	likely pathogenic
REVEL	0.178	moderately benign-leaning
SaProt	LLR -6.44	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 8,606 bp · p 0.0016 · regional, not allelic
Overall
CADD	24.2	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: CIPC
Protein: p.Val120Leu
Coding: c.358G>T
MANE Select: NM_033426
Type: single nucleotide variant
Location: chr14:77113476 (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-val120leu (accessed [today's date]).

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