Is ASAP2 p.Ala592= (c.1776A>G) pathogenic?

ASAP2 p.Ala592= (c.1776A>G) is classified Benign in ASAP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-01-22). Low-frequency (popmax 1.29%, nfe).

How common is ASAP2 p.Ala592= (c.1776A>G) in the general population?

ASAP2 p.Ala592= (c.1776A>G) is low-frequency (popmax 1.29%, nfe) (gnomAD).

ASAP2 p.Ala592=

c.1776A>G · rs34464740 · VCV774808

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.29%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -4.4
Overall
CADD	0.338	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.29% European (non-Finnish) · 15,219/1,179,970 alleles

Filtering AF 1.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.27%

Overall 1.09% 17,659/1,614,124 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.46%	69
European (non-Finnish)grpmax	1.29%	78
Remaining individualsnot grpmax-eligible	0.853%	117
South Asian	0.527%	190
Ashkenazi Jewishnot grpmax-eligible	0.51%	196
Middle Eastern	0.313%	319
Admixed American	0.29%	345
African / African-American	0.196%	511
Amishnot grpmax-eligible	0.11%	912
East Asian	0.00446%	22,441

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala592=
Coding: c.1776A>G
MANE Select: NM_003887
dbSNP: rs34464740
Type: single nucleotide variant
Location: chr2:9376937 (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.Ala592Val Uncertain significance ★ ⚠ same residue
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-ala592 (accessed [today's date]).

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