Is CAAP1 p.Asn314His (c.940A>C) pathogenic?

CAAP1 p.Asn314His (c.940A>C) is classified Uncertain significance in CAAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: likely benign (0.0644); Very rare (popmax 0.0028%, nfe).

How common is CAAP1 p.Asn314His (c.940A>C) in the general population?

CAAP1 p.Asn314His (c.940A>C) is very rare (popmax 0.0028%, nfe) (gnomAD).

What do computational predictors say about CAAP1 p.Asn314His (c.940A>C)?

AlphaMissense predicts likely benign (score 0.0644) — an in-silico prediction, not a clinical call.

CAAP1 p.Asn314His

c.940A>C · rs149224304 · VCV3136168

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0644 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0028%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0644	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -6.85	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 0.32	GERP -2.2, phastCons 0.81
Regional constraint	o/e 1.26	unconstrained · MANE · 50 kb · p 1.7e-07 · regional, not allelic
Overall
CADD	16.64	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 0.0028% European (non-Finnish) · 33/1,180,046 alleles

Filtering AF 0.00199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00175%

Overall 0.00204% 33/1,614,048 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: CAAP1
Protein: p.Asn314His
Coding: c.940A>C
MANE Select: NM_024828
dbSNP: rs149224304
Type: single nucleotide variant
Location: chr9:26842447 (GRCh38)
Gene constraint: LOEUF 1.136 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.18
Residue 314: 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-asn314his (accessed [today's date]).

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