Is CLIP1 p.Ala202Pro (c.604G>C) pathogenic?

CLIP1 p.Ala202Pro (c.604G>C) is classified Likely benign in CLIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-09). AlphaMissense: ambiguous (0.4571); Rare (popmax 0.259%, afr).

How common is CLIP1 p.Ala202Pro (c.604G>C) in the general population?

CLIP1 p.Ala202Pro (c.604G>C) is rare (popmax 0.259%, afr) (gnomAD).

What do computational predictors say about CLIP1 p.Ala202Pro (c.604G>C)?

AlphaMissense predicts ambiguous (score 0.4571) — an in-silico prediction, not a clinical call.

CLIP1 p.Ala202Pro

c.604G>C · rs140634925 · VCV711098

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4571 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.259%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4571	ambiguous
REVEL	0.252	benign-leaning
SaProt	LLR -8.37	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP -0.098, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 273 bp · p 0.51 · regional, not allelic
Overall
CADD	22.5	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 0.259% African / African-American · 194/75,030 alleles

Filtering AF 0.229% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.217%

Overall 0.0152% 246/1,614,116 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.259%	387
Remaining individualsnot grpmax-eligible	0.032%	3,125
Admixed American	0.0167%	5,999
Middle Eastern	0.0165%	6,062
South Asian	0.00549%	18,217
European (non-Finnish)	0.00136%	73,751

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: CLIP1
Protein: p.Ala202Pro
Coding: c.604G>C
MANE Select: NM_001247997
dbSNP: rs140634925
Type: single nucleotide variant
Location: chr12:122377442 (GRCh38)
Gene constraint: LOEUF 0.455 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.16 · 11 PDB

Full CLIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLIP1 p.Ala142Val Uncertain significance ★★ ⚠ same type
CLIP1 p.Arg342Cys Uncertain significance ★★ ⚠ same type
CLIP1 p.Gly1356Arg Uncertain significance ★★ ⚠ same type
CLIP1 p.Lys1267Arg Uncertain significance ★★ ⚠ same type
CLIP1 p.Ala1224Ser Likely benign ★★ same type
CLIP1 p.Ala301= Benign ★★ same type
CLIP1 p.Asn99= Benign/Likely benign ★★ same type
CLIP1 p.Lys851= Likely benign ★★ 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/clip1-p-ala202pro (accessed [today's date]).

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