Is ADAP1 p.Asp331Asn (c.991G>A) pathogenic?

ADAP1 p.Asp331Asn (c.991G>A) is classified Uncertain significance in ADAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-09). AlphaMissense: likely benign (0.2902); Very rare (popmax 0.00446%, eas).

How common is ADAP1 p.Asp331Asn (c.991G>A) in the general population?

ADAP1 p.Asp331Asn (c.991G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about ADAP1 p.Asp331Asn (c.991G>A)?

AlphaMissense predicts likely benign (score 0.2902) — an in-silico prediction, not a clinical call.

ADAP1 p.Asp331Asn

c.991G>A · rs1258238111 · VCV2294544

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2902 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2902	likely benign
REVEL	0.165	moderately benign-leaning
SaProt	LLR -7.88	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 7.4	GERP 4.1, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 56 kb · p 0.32 · regional, not allelic
Overall
CADD	24.7	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 0.00446% East Asian · 2/44,892 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00143% 23/1,610,208 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00829%	12,058
East Asiangrpmax	0.00446%	22,446
South Asian	0.00329%	30,360
Remaining individualsnot grpmax-eligible	0.0016%	62,446
European (non-Finnish)	0.00102%	98,330

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: ADAP1
Protein: p.Asp331Asn
Coding: c.991G>A
MANE Select: NM_006869
dbSNP: rs1258238111
Type: single nucleotide variant
Location: chr7:899138 (GRCh38)
Gene constraint: LOEUF 0.949 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.96 · 4 PDB
Residue 331: the ph 2 domain

Full ADAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAP1 p.Ala168Val Uncertain significance ★ ⚠ same type
ADAP1 p.Ala182Thr Uncertain significance ★ same type
ADAP1 p.Ala243Thr Uncertain significance ★ ⚠ same type
ADAP1 p.Ala26Val Uncertain significance ★ ⚠ same type
ADAP1 p.Ala293Val Uncertain significance ★ ⚠ same type
ADAP1 p.Ala349Val Uncertain significance ★ ⚠ same type
ADAP1 p.Ala81Glu Uncertain significance ★ ⚠ same type
ADAP1 p.Ala81Val 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/adap1-p-asp331asn (accessed [today's date]).

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