Is CAPS p.Ser172Ala (c.514T>G) pathogenic?

CAPS p.Ser172Ala (c.514T>G) is classified Uncertain significance in CAPS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-21). AlphaMissense: likely benign (0.1238); Ultra-rare (popmax 0.0481%, afr).

How common is CAPS p.Ser172Ala (c.514T>G) in the general population?

CAPS p.Ser172Ala (c.514T>G) is ultra-rare (popmax 0.0481%, afr) (gnomAD).

What do computational predictors say about CAPS p.Ser172Ala (c.514T>G)?

AlphaMissense predicts likely benign (score 0.1238) — an in-silico prediction, not a clinical call.

CAPS p.Ser172Ala

c.514T>G · VCV3484910

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1238 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0481%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1238	likely benign
REVEL	0.282	benign-leaning
SaProt	LLR -7.46	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 6	GERP 1.9, phastCons 1
Overall
CADD	20.9	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S258A vs ClinVar S172A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0481% African / African-American · 36/74,864 alleles

Filtering AF 0.0357% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0314%

Overall 0.00267% 43/1,612,868 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0481%	2,080
Admixed American	0.005%	19,990
Remaining individualsnot grpmax-eligible	0.0048%	20,817
European (non-Finnish)	8.48e-05%	1,179,889

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: CAPS
Protein: p.Ser172Ala
Coding: c.514T>G
MANE Select: NM_003716 · reported on NM_004058
Type: single nucleotide variant
Location: chr19:5915266 (GRCh38)
Structure: AlphaFold pLDDT 79.13 · 1 PDB

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

Similar variants

CADPS p.Ser203= Benign ★★ same type
CADPS p.Tyr579= Benign ★★ same type
CAPS p.Arg18His Benign ★★ ⚠ same type
CAPS p.Pro88Thr Benign ★★ ⚠ same type
CADPS c.3477+2T>G Uncertain significance ★ same type
CADPS p.Ala1047Thr Uncertain significance ★ ⚠ same type
CADPS p.Ala1057Val Uncertain significance ★ ⚠ same type
CADPS p.Ala1114Thr 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/caps-p-ser172ala (accessed [today's date]).

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