Is CAPSL p.Asp60Ala (c.179A>C) pathogenic?

CAPSL p.Asp60Ala (c.179A>C) is classified Uncertain significance in CAPSL (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-05). AlphaMissense: ambiguous (0.4735); Ultra-rare (popmax 0.015%, amr).

How common is CAPSL p.Asp60Ala (c.179A>C) in the general population?

CAPSL p.Asp60Ala (c.179A>C) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about CAPSL p.Asp60Ala (c.179A>C)?

AlphaMissense predicts ambiguous (score 0.4735) — an in-silico prediction, not a clinical call.

CAPSL p.Asp60Ala

c.179A>C · rs201588644 · VCV2349136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4735 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4735	ambiguous
REVEL	0.773	moderately pathogenic-leaning
SaProt	LLR -12.69	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.53 · evaluated, not missing
Pangolin	Δ0.25	gain · loss 0.12 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 5.1	GERP 1.6, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 17 kb · p 0.065 · regional, not allelic
Overall
CADD	24.7	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 0.015% Admixed American · 9/59,904 alleles

Filtering AF 0.00774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00273% 44/1,612,138 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0203%	4,919
Admixed Americangrpmax	0.015%	6,656
European (non-Finnish)	0.00187%	53,580

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CAPSL
Protein: p.Asp60Ala
Coding: c.179A>C
MANE Select: NM_001042625
dbSNP: rs201588644
Type: single nucleotide variant
Location: chr5:35910502 (GRCh38)
Gene constraint: LOEUF 1.17 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.88 · 1 PDB
Residue 60: the ef-hand 1 domain

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

Similar variants

CAPSL p.Phe61Val Uncertain significance ★★ ⚠ same type
CAPSL p.Met201Val Benign ★★ ⚠ same type
CAPSL p.Ala2Ser Uncertain significance ★ ⚠ same type
CAPSL p.Arg137Cys Uncertain significance ★ ⚠ same type
CAPSL p.Arg137His Uncertain significance ★ ⚠ same type
CAPSL p.Arg137Leu Uncertain significance ★ ⚠ same type
CAPSL p.Arg160Thr Uncertain significance ★ ⚠ same type
CAPSL p.Asp135Glu 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/capsl-p-asp60ala (accessed [today's date]).

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