Is ACAP2 p.Ser601Leu (c.1802C>T) pathogenic?

ACAP2 p.Ser601Leu (c.1802C>T) is classified Uncertain significance in ACAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: likely benign (0.0783); Ultra-rare (popmax 0.0662%, mid).

How common is ACAP2 p.Ser601Leu (c.1802C>T) in the general population?

ACAP2 p.Ser601Leu (c.1802C>T) is ultra-rare (popmax 0.0662%, mid) (gnomAD).

What do computational predictors say about ACAP2 p.Ser601Leu (c.1802C>T)?

AlphaMissense predicts likely benign (score 0.0783) — an in-silico prediction, not a clinical call.

ACAP2 p.Ser601Leu

c.1802C>T · VCV4214762

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0783 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0662%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0783	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -6.75	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 7.4	GERP 1.8, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 3,487 bp · p 0.37 · regional, not allelic
Overall
CADD	23.7	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 0.0662% Middle Eastern · 4/6,046 alleles

Filtering AF 0.0379% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.033%

Overall 0.0117% 188/1,611,172 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0662%	1,512
Admixed American	0.0524%	1,907
Remaining individualsnot grpmax-eligible	0.024%	4,159
European (non-Finnish)	0.0113%	8,867
African / African-American	0.00268%	37,351
East Asian	0.00223%	44,844
South Asian	0.00221%	45,226

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: ACAP2
Protein: p.Ser601Leu
Coding: c.1802C>T
MANE Select: NM_012287
Type: single nucleotide variant
Location: chr3:195292416 (GRCh38)
Gene constraint: LOEUF 0.47 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.71 · 1 PDB

Full ACAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACAP2 c.53+1G>A Uncertain significance ★ same type
ACAP2 p.Arg167Gln Uncertain significance ★ ⚠ same type
ACAP2 p.Arg226Gln Uncertain significance ★ ⚠ same type
ACAP2 p.Arg287His Uncertain significance ★ ⚠ same type
ACAP2 p.Arg404Gln Uncertain significance ★ ⚠ same type
ACAP2 p.Arg755His Uncertain significance ★ ⚠ same type
ACAP2 p.Asn265His Uncertain significance ★ ⚠ same type
ACAP2 p.Asn265Ser 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/acap2-p-ser601leu (accessed [today's date]).

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