Is ACAP1 p.Arg551Trp (c.1651C>T) pathogenic?

ACAP1 p.Arg551Trp (c.1651C>T) is classified Uncertain significance in ACAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.1204); Ultra-rare (popmax 0.0156%, amr).

How common is ACAP1 p.Arg551Trp (c.1651C>T) in the general population?

ACAP1 p.Arg551Trp (c.1651C>T) is ultra-rare (popmax 0.0156%, amr) (gnomAD).

What do computational predictors say about ACAP1 p.Arg551Trp (c.1651C>T)?

AlphaMissense predicts likely benign (score 0.1204) — an in-silico prediction, not a clinical call.

ACAP1 p.Arg551Trp

c.1651C>T · rs760206336 · VCV3135502

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1204 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1204	likely benign
REVEL	0.173	moderately benign-leaning
SaProt	LLR -10.47	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.29	GERP -1.3
Regional constraint	o/e 1.24	unconstrained · MANE · 661 bp · p 0.052 · regional, not allelic
Overall
CADD	20.1	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 0.0156% Admixed American · 6/38,564 alleles

Filtering AF 0.00677% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00455%

Overall 0.0041% 61/1,488,928 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0156%	6,427
European (non-Finnish)	0.00464%	21,534
Remaining individualsnot grpmax-eligible	0.00175%	57,180
African / African-American	0.0014%	71,226
South Asian	0.0014%	71,632

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.Arg551Trp
Coding: c.1651C>T
MANE Select: NM_014716
dbSNP: rs760206336
Type: single nucleotide variant
Location: chr17:7348448 (GRCh38)
Gene constraint: LOEUF 0.579 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.92 · 7 PDB
Residue 551: the 'disordered' region; the 'prevents interaction with itgb1 when s-554 is not phosphorylated' region; the 'required for interaction with gulp1' region

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

Similar variants

ACAP1 p.Arg551Pro Uncertain significance ★ ⚠ same residue
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.Ala58Asp Uncertain significance ★ ⚠ same type
ACAP1 p.Ala596Thr Uncertain significance ★ ⚠ same type
ACAP1 p.Ala636Glu 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-arg551trp (accessed [today's date]).

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