Is CAAP1 p.Ser7Phe (c.20C>T) pathogenic?

CAAP1 p.Ser7Phe (c.20C>T) is classified Uncertain significance in CAAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely pathogenic (0.7748); Very rare (popmax 0.00223%, eas).

How common is CAAP1 p.Ser7Phe (c.20C>T) in the general population?

CAAP1 p.Ser7Phe (c.20C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CAAP1 p.Ser7Phe (c.20C>T)?

AlphaMissense predicts likely pathogenic (score 0.7748) — an in-silico prediction, not a clinical call.

CAAP1 p.Ser7Phe

c.20C>T · rs267602204 · VCV4217567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7748 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7748	likely pathogenic
REVEL	0.231	benign-leaning
SaProt	LLR -2.80	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 50 kb · p 1.7e-07 · regional, not allelic
Overall
CADD	25.5	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 0.00223% East Asian · 1/44,760 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00025% 4/1,600,030 alleles · very rare exomes 2/1,447,786 · genomes 2/152,244 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,760
European (non-Finnish)	0.000255%	392,268

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.Ser7Phe
Coding: c.20C>T
MANE Select: NM_024828
dbSNP: rs267602204
Type: single nucleotide variant
Location: chr9:26892696 (GRCh38)
Gene constraint: LOEUF 1.136 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.18
Residue 7: 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-ser7phe (accessed [today's date]).

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