Is CAAP1 p.Ser53Thr (c.158G>C) pathogenic?

CAAP1 p.Ser53Thr (c.158G>C) is classified Likely benign in CAAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-28). AlphaMissense: likely benign (0.0645); Very rare (popmax 0.00574%, nfe).

How common is CAAP1 p.Ser53Thr (c.158G>C) in the general population?

CAAP1 p.Ser53Thr (c.158G>C) is very rare (popmax 0.00574%, nfe) (gnomAD).

What do computational predictors say about CAAP1 p.Ser53Thr (c.158G>C)?

AlphaMissense predicts likely benign (score 0.0645) — an in-silico prediction, not a clinical call.

CAAP1 p.Ser53Thr

c.158G>C · VCV3826477

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0645 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00574%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0645	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -8.75	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 2.7	GERP -0.83, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 50 kb · p 1.7e-07 · regional, not allelic
Overall
CADD	17.32	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 0.00574% European (non-Finnish) · 67/1,166,766 alleles

Filtering AF 0.00459% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00422%

Overall 0.00441% 70/1,586,108 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00574%	17,414
Remaining individualsnot grpmax-eligible	0.00325%	30,745
African / African-American	0.00134%	74,460

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: CAAP1
Protein: p.Ser53Thr
Coding: c.158G>C
MANE Select: NM_024828
Type: single nucleotide variant
Location: chr9:26892558 (GRCh38)
Gene constraint: LOEUF 1.136 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.18

Full CAAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAAP1 p.Ala209Val Uncertain significance ★ ⚠ same type
CAAP1 p.Ala22Glu Uncertain significance ★ ⚠ same type
CAAP1 p.Ala261Gly Uncertain significance ★ ⚠ same type
CAAP1 p.Ala288Gly Uncertain significance ★ ⚠ same type
CAAP1 p.Ala322Ser Uncertain significance ★ ⚠ same type
CAAP1 p.Ala347Pro Uncertain significance ★ ⚠ same type
CAAP1 p.Ala354Pro Uncertain significance ★ ⚠ same type
CAAP1 p.Arg12Gly 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/caap1-p-ser53thr (accessed [today's date]).

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