Is ADD2 p.Ser530Arg (c.1590C>G) pathogenic?

ADD2 p.Ser530Arg (c.1590C>G) is classified Uncertain significance in ADD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). AlphaMissense: likely pathogenic (0.8032); Absent from gnomAD v4.1.

How common is ADD2 p.Ser530Arg (c.1590C>G) in the general population?

ADD2 p.Ser530Arg (c.1590C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADD2 p.Ser530Arg (c.1590C>G)?

AlphaMissense predicts likely pathogenic (score 0.8032) — an in-silico prediction, not a clinical call.

ADD2 p.Ser530Arg

c.1590C>G · VCV3495547

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8032 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8032	likely pathogenic
REVEL	0.157	moderately benign-leaning
SaProt	LLR -6.75	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	Δ0.21	donor loss, 3 bp away · masked 0 · deltas
Pangolin	Δ0.29	loss · gain 0.10 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.3	GERP -3.1, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 21 kb · p 3.2e-07 · regional, not allelic
Overall
CADD	18.31	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ADD2
Protein: p.Ser530Arg
Coding: c.1590C>G
MANE Select: NM_001617
Type: single nucleotide variant
Location: chr2:70676799 (GRCh38)
Gene constraint: LOEUF 0.388 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.51
Residue 530: a modified residue (phosphoserine); the 'disordered' region

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-ser530arg (accessed [today's date]).

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