Is CABP4 p.Pro74Thr (c.220C>A) pathogenic?

CABP4 p.Pro74Thr (c.220C>A) is classified Uncertain significance in CABP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-30). AlphaMissense: likely benign (0.0611); Very rare (popmax 0.000763%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CABP4 p.Pro74Thr (c.220C>A)?

CABP4 p.Pro74Thr (c.220C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CABP4 p.Pro74Thr (c.220C>A) in the general population?

CABP4 p.Pro74Thr (c.220C>A) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about CABP4 p.Pro74Thr (c.220C>A)?

AlphaMissense predicts likely benign (score 0.0611) — an in-silico prediction, not a clinical call.

CABP4 p.Pro74Thr

c.220C>A · rs781765153 · VCV2299322

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0611 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0611	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -6.78	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 -0.93	GERP -4
Regional constraint	o/e 1.07	unconstrained · MANE · 3,232 bp · p 0.15 · regional, not allelic
Overall
CADD	0.326	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 0.000763% European (non-Finnish) · 9/1,179,256 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000617% 9/1,457,928 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: CABP4
Protein: p.Pro74Thr
Coding: c.220C>A
MANE Select: NM_145200
dbSNP: rs781765153
Type: single nucleotide variant
Location: chr11:67455643 (GRCh38)
Gene constraint: LOEUF 1.345 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.01
Residue 74: the 'disordered' region

Full CABP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CABP4 p.Pro74Ser Uncertain significance ★ same residue
CABP4 p.Ala107Thr Uncertain significance ★★ ⚠ same condition
CABP4 p.Ala108Thr Uncertain significance ★★ ⚠ same condition
CABP4 p.Ala137Thr Uncertain significance ★★ ⚠ same condition
CABP4 p.Ala203Val Uncertain significance ★★ ⚠ same condition
CABP4 p.Ala229Val Uncertain significance ★★ ⚠ same condition
CABP4 p.Ala234Val Uncertain significance ★★ ⚠ same condition
CABP4 p.Arg152Trp Uncertain significance ★★ ⚠ same condition

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/cabp4-p-pro74thr (accessed [today's date]).

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