Is CLIP3 p.Pro13Ser (c.37C>T) pathogenic?

CLIP3 p.Pro13Ser (c.37C>T) is classified Uncertain significance in CLIP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely benign (0.0715); Absent from gnomAD v4.1.

How common is CLIP3 p.Pro13Ser (c.37C>T) in the general population?

CLIP3 p.Pro13Ser (c.37C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLIP3 p.Pro13Ser (c.37C>T)?

AlphaMissense predicts likely benign (score 0.0715) — an in-silico prediction, not a clinical call.

CLIP3 p.Pro13Ser

c.37C>T · VCV4003702

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0715 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,276,708)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0715	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -6.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 5,154 bp · p 0.14 · regional, not allelic
Overall
CADD	21.8	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

No allele count reported in gnomAD v4.1 (AN 1,276,708). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CLIP3
Protein: p.Pro13Ser
Coding: c.37C>T
MANE Select: NM_015526
Type: single nucleotide variant
Location: chr19:36032321 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.93 · 1 PDB
Residue 13: the 'disordered' region

Full CLIP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLIP3 p.Ala137Val Uncertain significance ★ ⚠ same type
CLIP3 p.Ala148Val Uncertain significance ★ ⚠ same type
CLIP3 p.Ala214Thr Uncertain significance ★ ⚠ same type
CLIP3 p.Ala225Val Uncertain significance ★ ⚠ same type
CLIP3 p.Ala251Val Uncertain significance ★ ⚠ same type
CLIP3 p.Ala271Thr Uncertain significance ★ ⚠ same type
CLIP3 p.Ala30Ser Uncertain significance ★ ⚠ same type
CLIP3 p.Ala7Thr 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/clip3-p-pro13ser (accessed [today's date]).

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