Is ADD2 p.Asp28Asn (c.82G>A) pathogenic?

ADD2 p.Asp28Asn (c.82G>A) is classified Benign in ADD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-18). AlphaMissense: likely benign (0.1564); Common (popmax 6.75%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about ADD2 p.Asp28Asn (c.82G>A)?

AlphaMissense predicts likely benign (score 0.1564) — an in-silico prediction, not a clinical call.

ADD2 p.Asp28Asn

Q: How common is ADD2 p.Asp28Asn (c.82G>A) in the general population?

ADD2 p.Asp28Asn (c.82G>A) is common (popmax 6.75%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.82G>A · rs4986 · VCV783975

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1564 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.75%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1564	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -7.80	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 6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 10 kb · p 0.22 · regional, not allelic
Overall
CADD	24.2	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 6.75% African / African-American · 5,068/75,044 alleles

Filtering AF 6.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.53%

Overall 0.357% 5,764/1,613,988 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.75%	15
Middle Eastern	0.611%	164
Remaining individualsnot grpmax-eligible	0.459%	218
Admixed American	0.377%	266
South Asian	0.0132%	7,589
European (non-Finnish)	0.0113%	8,872
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604

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: ADD2
Protein: p.Asp28Asn
Coding: c.82G>A
MANE Select: NM_001617
dbSNP: rs4986
Type: single nucleotide variant
Location: chr2:70706327 (GRCh38)
Gene constraint: LOEUF 0.388 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.51
Residue 28: a UniProt-annotated variant site (in)

Full ADD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADD2 p.Glu335Asp Benign ★★ same type
ADD2 p.Gly17Glu Benign ★★ same type
ADD2 p.Ala150Val Uncertain significance ★ ⚠ same type
ADD2 p.Ala232Gly Uncertain significance ★ ⚠ same type
ADD2 p.Ala312Thr Uncertain significance ★ ⚠ same type
ADD2 p.Ala418Pro Uncertain significance ★ ⚠ same type
ADD2 p.Ala606Val Uncertain significance ★ ⚠ same type
ADD2 p.Ala609Thr 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/add2-p-asp28asn (accessed [today's date]).

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