Is ADD2 p.Arg384Cys (c.1150C>T) pathogenic?

ADD2 p.Arg384Cys (c.1150C>T) is classified Uncertain significance in ADD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: likely benign (0.3082); Very rare (popmax 0.00134%, afr).

How common is ADD2 p.Arg384Cys (c.1150C>T) in the general population?

ADD2 p.Arg384Cys (c.1150C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about ADD2 p.Arg384Cys (c.1150C>T)?

AlphaMissense predicts likely benign (score 0.3082) — an in-silico prediction, not a clinical call.

ADD2 p.Arg384Cys

c.1150C>T · VCV4236774

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3082 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3082	likely benign
REVEL	0.584	indeterminate
SaProt	LLR -12.82	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.56, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 21 kb · p 3.2e-07 · regional, not allelic
Overall
CADD	33.0	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 0.00134% African / African-American · 1/74,906 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,330 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,906
European (non-Finnish)	0.00017%	589,845

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.Arg384Cys
Coding: c.1150C>T
MANE Select: NM_001617
Type: single nucleotide variant
Location: chr2:70678937 (GRCh38)
Gene constraint: LOEUF 0.388 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.51

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

Similar variants

ADD2 p.Asp28Asn Benign ★★ same type
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

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-arg384cys (accessed [today's date]).

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