Is ASAP2 p.Ala735Thr (c.2203G>A) pathogenic?

ASAP2 p.Ala735Thr (c.2203G>A) is classified Uncertain significance in ASAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). AlphaMissense: likely benign (0.0674); Very rare (popmax 0.00737%, nfe).

How common is ASAP2 p.Ala735Thr (c.2203G>A) in the general population?

ASAP2 p.Ala735Thr (c.2203G>A) is very rare (popmax 0.00737%, nfe) (gnomAD).

What do computational predictors say about ASAP2 p.Ala735Thr (c.2203G>A)?

AlphaMissense predicts likely benign (score 0.0674) — an in-silico prediction, not a clinical call.

ASAP2 p.Ala735Thr

c.2203G>A · rs201291876 · VCV3130047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0674 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00737%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0674	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -6.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.55	GERP -3.2, phastCons 0.002
Regional constraint	o/e 0.93	unconstrained · MANE · 44 kb · p 0.076 · regional, not allelic
Overall
CADD	12.46	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 0.00737% European (non-Finnish) · 87/1,180,044 alleles

Filtering AF 0.00605% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00565%

Overall 0.0057% 92/1,614,000 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00737%	13,564
Remaining individualsnot grpmax-eligible	0.0048%	20,829
East Asian	0.00223%	44,888
Admixed American	0.00167%	59,982

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.Ala735Thr
Coding: c.2203G>A
MANE Select: NM_003887
dbSNP: rs201291876
Type: single nucleotide variant
Location: chr2:9388366 (GRCh38)
Gene constraint: LOEUF 0.465 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.71

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

Similar variants

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
ASAP2 p.Ala31Val 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-ala735thr (accessed [today's date]).

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