Is CLIP2 p.Ser182Thr (c.545G>C) pathogenic?

CLIP2 p.Ser182Thr (c.545G>C) is classified Uncertain significance in CLIP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-10). AlphaMissense: likely benign (0.0775); Very rare (popmax 0.00333%, amr).

How common is CLIP2 p.Ser182Thr (c.545G>C) in the general population?

CLIP2 p.Ser182Thr (c.545G>C) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CLIP2 p.Ser182Thr (c.545G>C)?

AlphaMissense predicts likely benign (score 0.0775) — an in-silico prediction, not a clinical call.

CLIP2 p.Ser182Thr

c.545G>C · VCV3834029

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0775 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0775	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -7.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 6.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 21 kb · p 0.42 · regional, not allelic
Overall
CADD	20.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00333% Admixed American · 2/59,996 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00124% 20/1,607,824 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,998
European (non-Finnish)	0.00153%	65,551

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: CLIP2
Protein: p.Ser182Thr
Coding: c.545G>C
MANE Select: NM_003388
Type: single nucleotide variant
Location: chr7:74338871 (GRCh38)
Gene constraint: LOEUF 0.476 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 75.25 · 2 PDB

Full CLIP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLIP2 p.Arg12His Uncertain significance ★★ ⚠ same type
CLIP2 p.Ala123= Benign ★★ same type
CLIP2 p.Arg932= Benign ★★ same type
CLIP2 p.Asn205= Benign ★★ same type
CLIP2 p.Asn910= Benign/Likely benign ★★ same type
CLIP2 p.His159= Benign/Likely benign ★★ same type
CLIP2 p.Ile396= Benign ★★ same type
CLIP2 p.Leu169= 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/clip2-p-ser182thr (accessed [today's date]).

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