Is CLIP4 p.Ser350Arg (c.1048A>C) pathogenic?

CLIP4 p.Ser350Arg (c.1048A>C) is classified Uncertain significance in CLIP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-24). AlphaMissense: likely pathogenic (0.686); Very rare (popmax 0.0022%, sas).

How common is CLIP4 p.Ser350Arg (c.1048A>C) in the general population?

CLIP4 p.Ser350Arg (c.1048A>C) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CLIP4 p.Ser350Arg (c.1048A>C)?

AlphaMissense predicts likely pathogenic (score 0.686) — an in-silico prediction, not a clinical call.

CLIP4 p.Ser350Arg

c.1048A>C · rs1666654882 · VCV2551389

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.686 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.686	likely pathogenic
REVEL	0.517	indeterminate
SaProt	LLR -8.13	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Overall
CADD	26.9	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 0.0022% South Asian · 2/90,990 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,461,266 alleles · very rare

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: CLIP4
Protein: p.Ser350Arg
Coding: c.1048A>C
MANE Select: NM_018961 · reported on NM_024692
dbSNP: rs1666654882
Type: single nucleotide variant
Location: chr2:29152711 (GRCh38)
Structure: AlphaFold pLDDT 82.62 · 2 PDB

Full CLIP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UBASH3A p.Ile463Phe Uncertain significance ★★ ⚠ same type
CLIP4 p.Thr555= Benign ★★ same type
UBASH3A c.1393+3A>C Benign ★★ same type
UBASH3A p.Gly601= Benign ★★ same type
UBASH3A p.Ile303= Benign ★★ same type
UBASH3A p.Ile658Val Benign ★★ same type
UBASH3A p.Phe304= Benign ★★ same type
UBASH3A p.Thr144= 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/clip4-p-ser350arg (accessed [today's date]).

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