Is ACAP3 p.Pro806Ser (c.2416C>T) pathogenic?

ACAP3 p.Pro806Ser (c.2416C>T) is classified Uncertain significance in ACAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). AlphaMissense: likely benign (0.0621); Very rare (popmax 0.00255%, sas).

How common is ACAP3 p.Pro806Ser (c.2416C>T) in the general population?

ACAP3 p.Pro806Ser (c.2416C>T) is very rare (popmax 0.00255%, sas) (gnomAD).

What do computational predictors say about ACAP3 p.Pro806Ser (c.2416C>T)?

AlphaMissense predicts likely benign (score 0.0621) — an in-silico prediction, not a clinical call.

ACAP3 p.Pro806Ser

c.2416C>T · VCV3997263

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0621 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00255%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0621	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -6.17	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 9.5	GERP 2.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 14 kb · p 0.33 · regional, not allelic
Overall
CADD	19.6	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 0.00255% South Asian · 2/78,486 alleles

Filtering AF 0.000423% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000158%

Overall 0.000679% 9/1,324,954 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00255%	39,243
Remaining individualsnot grpmax-eligible	0.00176%	56,868
European (non-Finnish)	0.000535%	187,033

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: ACAP3
Protein: p.Pro806Ser
Coding: c.2416C>T
MANE Select: NM_030649
Type: single nucleotide variant
Location: chr1:1293653 (GRCh38)
Gene constraint: LOEUF 0.816 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.31

Full ACAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACAP3 p.Pro806Thr Uncertain significance ★ ⚠ same residue
ACAP3 p.Ala242Val Uncertain significance ★ ⚠ same type
ACAP3 p.Ala265Val Uncertain significance ★ ⚠ same type
ACAP3 p.Ala282Thr Uncertain significance ★ ⚠ same type
ACAP3 p.Ala307Thr Uncertain significance ★ ⚠ same type
ACAP3 p.Ala392Thr Uncertain significance ★ ⚠ same type
ACAP3 p.Ala526Thr Uncertain significance ★ ⚠ same type
ACAP3 p.Ala596Val 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/acap3-p-pro806ser (accessed [today's date]).

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