Is CAAP1 p.Ala230Thr (c.688G>A) pathogenic?

CAAP1 p.Ala230Thr (c.688G>A) is classified Likely benign in CAAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-13). AlphaMissense: likely benign (0.0569); Rare (popmax 0.146%, afr).

How common is CAAP1 p.Ala230Thr (c.688G>A) in the general population?

CAAP1 p.Ala230Thr (c.688G>A) is rare (popmax 0.146%, afr) (gnomAD).

What do computational predictors say about CAAP1 p.Ala230Thr (c.688G>A)?

AlphaMissense predicts likely benign (score 0.0569) — an in-silico prediction, not a clinical call.

CAAP1 p.Ala230Thr

c.688G>A · rs141753758 · VCV2456111

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0569 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.146%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0569	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -6.13	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 -0.66	GERP -3.5, phastCons 0.029
Regional constraint	o/e 1.26	unconstrained · MANE · 50 kb · p 1.7e-07 · regional, not allelic
Overall
CADD	0.39	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 0.146% African / African-American · 109/74,720 alleles

Filtering AF 0.124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.115%

Overall 0.00807% 130/1,610,932 alleles · rare exomes 62/1,458,802 · genomes 68/152,130 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.146%	686
Middle Eastern	0.0165%	6,064
Remaining individualsnot grpmax-eligible	0.0128%	7,796
Admixed American	0.00167%	59,958
European (non-Finnish)	0.000934%	107,058

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.Ala230Thr
Coding: c.688G>A
MANE Select: NM_024828
dbSNP: rs141753758
Type: single nucleotide variant
Location: chr9:26861117 (GRCh38)
Gene constraint: LOEUF 1.136 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.18
Residue 230: the 'disordered' region

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-ala230thr (accessed [today's date]).

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