Is ASAP2 p.Asp718Glu (c.2154C>G) pathogenic?

ASAP2 p.Asp718Glu (c.2154C>G) is classified Uncertain significance in ASAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.113); Very rare (popmax 0.00356%, nfe).

How common is ASAP2 p.Asp718Glu (c.2154C>G) in the general population?

ASAP2 p.Asp718Glu (c.2154C>G) is very rare (popmax 0.00356%, nfe) (gnomAD).

What do computational predictors say about ASAP2 p.Asp718Glu (c.2154C>G)?

AlphaMissense predicts likely benign (score 0.113) — an in-silico prediction, not a clinical call.

ASAP2 p.Asp718Glu

c.2154C>G · rs150928429 · VCV2391700

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.113 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00356%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.113	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -5.35	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 2.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 44 kb · p 0.076 · regional, not allelic
Overall
CADD	19.4	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 0.00356% European (non-Finnish) · 42/1,180,044 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.00285% 46/1,614,022 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00356%	28,096
Remaining individualsnot grpmax-eligible	0.0032%	31,236
African / African-American	0.00267%	37,467

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.Asp718Glu
Coding: c.2154C>G
MANE Select: NM_003887
dbSNP: rs150928429
Type: single nucleotide variant
Location: chr2:9388317 (GRCh38)
Gene constraint: LOEUF 0.465 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.71
Residue 718: the 'disordered' region

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-asp718glu (accessed [today's date]).

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