Is CABP4 p.Arg274Cys (c.820C>T) pathogenic?

CABP4 p.Arg274Cys (c.820C>T) is classified Uncertain significance in CABP4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-09). AlphaMissense: likely benign (0.1383); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with CABP4 p.Arg274Cys (c.820C>T)?

CABP4 p.Arg274Cys (c.820C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CABP4 p.Arg274Cys (c.820C>T) in the general population?

CABP4 p.Arg274Cys (c.820C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CABP4 p.Arg274Cys (c.820C>T)?

AlphaMissense predicts likely benign (score 0.1383) — an in-silico prediction, not a clinical call.

CABP4 p.Arg274Cys

c.820C>T · rs202142799 · VCV1059055

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1383 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1383	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -10.41	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.046	GERP -4.2
Regional constraint	o/e 1.07	unconstrained · MANE · 3,232 bp · p 0.15 · regional, not allelic
Overall
CADD	18.11	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 0.00267% African / African-American · 2/74,912 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00186% 30/1,613,934 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
African / African-Americangrpmax	0.00267%	37,456
East Asian	0.00223%	44,906
European (non-Finnish)	0.00195%	51,306
Admixed American	0.00167%	59,992
Finnishnot grpmax-eligible	0.00156%	63,912
South Asian	0.0011%	91,090

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg274Cys
Coding: c.820C>T
MANE Select: NM_145200
dbSNP: rs202142799
Type: single nucleotide variant
Location: chr11:67458651 (GRCh38)
Gene constraint: LOEUF 1.345 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.01
Residue 274: the ef-hand 4 domain

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.Arg274Gly Benign/Likely benign ★★ ⚠ 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-arg274cys (accessed [today's date]).

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