Is ACAP1 p.Ala58Asp (c.173C>A) pathogenic?

ACAP1 p.Ala58Asp (c.173C>A) is classified Uncertain significance in ACAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-26). AlphaMissense: likely benign (0.2705); Very rare (popmax 0.00768%, sas).

How common is ACAP1 p.Ala58Asp (c.173C>A) in the general population?

ACAP1 p.Ala58Asp (c.173C>A) is very rare (popmax 0.00768%, sas) (gnomAD).

What do computational predictors say about ACAP1 p.Ala58Asp (c.173C>A)?

AlphaMissense predicts likely benign (score 0.2705) — an in-silico prediction, not a clinical call.

ACAP1 p.Ala58Asp

c.173C>A · rs370190619 · VCV3135516

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2705 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00768%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2705	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -8.52	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 4.8	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 10 kb · p 1e-05 · regional, not allelic
Overall
CADD	18.71	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 0.00768% South Asian · 7/91,090 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00229% 37/1,614,090 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00768%	13,013
African / African-American	0.00267%	37,464
East Asian	0.00223%	44,894
European (non-Finnish)	0.00212%	47,202
Remaining individualsnot grpmax-eligible	0.0016%	62,484
Finnishnot grpmax-eligible	0.00156%	64,038

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: ACAP1
Protein: p.Ala58Asp
Coding: c.173C>A
MANE Select: NM_014716
dbSNP: rs370190619
Type: single nucleotide variant
Location: chr17:7342009 (GRCh38)
Gene constraint: LOEUF 0.579 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.92 · 7 PDB
Residue 58: the bar domain; an α-helix; the 'required for formation of endosomal tubules when overexpressed with pip5k1c' region

Full ACAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACAP1 p.Val407Ala Uncertain significance ★★ ⚠ same type
ACAP1 p.Ala137Thr Uncertain significance ★ ⚠ same type
ACAP1 p.Ala418Asp Uncertain significance ★ ⚠ same type
ACAP1 p.Ala54Thr Uncertain significance ★ ⚠ same type
ACAP1 p.Ala596Thr Uncertain significance ★ ⚠ same type
ACAP1 p.Ala636Glu Uncertain significance ★ ⚠ same type
ACAP1 p.Ala636Val Uncertain significance ★ ⚠ same type
ACAP1 p.Ala656Ser 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/acap1-p-ala58asp (accessed [today's date]).

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