Is ASAP2 p.Arg719Gln (c.2156G>A) pathogenic?

ASAP2 p.Arg719Gln (c.2156G>A) is classified Uncertain significance in ASAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: ambiguous (0.4683); Very rare (popmax 0.00534%, afr).

How common is ASAP2 p.Arg719Gln (c.2156G>A) in the general population?

ASAP2 p.Arg719Gln (c.2156G>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about ASAP2 p.Arg719Gln (c.2156G>A)?

AlphaMissense predicts ambiguous (score 0.4683) — an in-silico prediction, not a clinical call.

ASAP2 p.Arg719Gln

c.2156G>A · VCV4151259

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4683 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Computational evidence

Protein change
AlphaMissense	0.4683	ambiguous
REVEL	0.322	indeterminate
SaProt	LLR -10.61	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 44 kb · p 0.076 · regional, not allelic
Overall
CADD	28.9	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 0.00534% African / African-American · 4/74,896 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00167% 27/1,613,894 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,724
European (non-Finnish)	0.00195%	51,305

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: ASAP2
Protein: p.Arg719Gln
Coding: c.2156G>A
MANE Select: NM_003887
Type: single nucleotide variant
Location: chr2:9388319 (GRCh38)
Gene constraint: LOEUF 0.465 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.71
Residue 719: the 'disordered' region

Full ASAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASAP2 p.Arg719Trp Uncertain significance ★ ⚠ same residue
ASAP2 p.Ala592= Benign ★★ same type
ASAP2 p.Asp434= Benign ★★ same type
ASAP2 p.Asp45= Benign ★★ same type
ASAP2 p.Pro868Leu Benign ★★ same type
ASAP2 c.687-1G>T Uncertain significance ★ same type
ASAP2 p.Ala1005Thr Uncertain significance ★ ⚠ same type
ASAP2 p.Ala276Thr 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/asap2-p-arg719gln (accessed [today's date]).

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