Is CLIP1 p.Arg342Cys (c.1024C>T) pathogenic?

CLIP1 p.Arg342Cys (c.1024C>T) is classified Uncertain significance in CLIP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-16). AlphaMissense: likely pathogenic (0.9124); Ultra-rare (popmax 0.0187%, afr).

How common is CLIP1 p.Arg342Cys (c.1024C>T) in the general population?

CLIP1 p.Arg342Cys (c.1024C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

What do computational predictors say about CLIP1 p.Arg342Cys (c.1024C>T)?

AlphaMissense predicts likely pathogenic (score 0.9124) — an in-silico prediction, not a clinical call.

CLIP1 p.Arg342Cys

c.1024C>T · rs149345437 · VCV839306

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9124 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9124	likely pathogenic
REVEL	0.428	indeterminate
SaProt	LLR -12.15	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 23 kb · p 9.8e-07 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0187% African / African-American · 14/74,942 alleles

Filtering AF 0.0113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0107%

Overall 0.0114% 184/1,613,878 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,353
Middle Eastern	0.0164%	6,080
Admixed American	0.0133%	7,498
European (non-Finnish)	0.013%	7,712
Remaining individualsnot grpmax-eligible	0.0064%	15,619
South Asian	0.00329%	30,355
East Asian	0.00223%	44,876

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.Arg342Cys
Coding: c.1024C>T
MANE Select: NM_001247997
dbSNP: rs149345437
Type: single nucleotide variant
Location: chr12:122355294 (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.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
CLIP1 p.Ser102= 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-arg342cys (accessed [today's date]).

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