Is ADAP2 p.Asp71His (c.211G>C) pathogenic?

ADAP2 p.Asp71His (c.211G>C) is classified Uncertain significance in ADAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-12). AlphaMissense: ambiguous (0.5227); Ultra-rare (popmax 0.0165%, mid).

How common is ADAP2 p.Asp71His (c.211G>C) in the general population?

ADAP2 p.Asp71His (c.211G>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ADAP2 p.Asp71His (c.211G>C)?

AlphaMissense predicts ambiguous (score 0.5227) — an in-silico prediction, not a clinical call.

ADAP2 p.Asp71His

c.211G>C · rs759687818 · VCV3080020

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5227 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Computational evidence

Protein change
AlphaMissense	0.5227	ambiguous
REVEL	0.335	indeterminate
SaProt	LLR -10.03	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 36 kb · p 0.019 · regional, not allelic
Overall
CADD	29.6	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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00661%

Overall 0.000958% 14/1,461,596 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
South Asian	0.0143%	7,005

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: ADAP2
Protein: p.Asp71His
Coding: c.211G>C
MANE Select: NM_018404
dbSNP: rs759687818
Type: single nucleotide variant
Location: chr17:30923056 (GRCh38)
Gene constraint: LOEUF 1.031 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.49
Residue 71: the arf-gap domain

Full ADAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAP2 p.Ala279Thr Uncertain significance ★ ⚠ same type
ADAP2 p.Ala36Ser Uncertain significance ★ ⚠ same type
ADAP2 p.Arg16Gly Uncertain significance ★ ⚠ same type
ADAP2 p.Arg209Lys Uncertain significance ★ ⚠ same type
ADAP2 p.Arg229His Uncertain significance ★ ⚠ same type
ADAP2 p.Arg254Lys Uncertain significance ★ ⚠ same type
ADAP2 p.Arg285Gln Uncertain significance ★ ⚠ same type
ADAP2 p.Arg322Gln 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/adap2-p-asp71his (accessed [today's date]).

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