Is DDB2 p.Gly232Ser (c.694G>A) pathogenic?

DDB2 p.Gly232Ser (c.694G>A) is classified Uncertain significance in DDB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-03). AlphaMissense: likely benign (0.2846); Very rare (popmax 0.00167%, amr).

How common is DDB2 p.Gly232Ser (c.694G>A) in the general population?

DDB2 p.Gly232Ser (c.694G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DDB2 p.Gly232Ser (c.694G>A)?

AlphaMissense predicts likely benign (score 0.2846) — an in-silico prediction, not a clinical call.

DDB2 p.Gly232Ser

c.694G>A · rs774675310 · VCV1319562

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2846 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2846	likely benign
REVEL	0.318	indeterminate
SaProt	LLR -8.28	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 0.081, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 24 kb · p 1.9e-07 · regional, not allelic
Overall
CADD	26.7	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 0.00167% Admixed American · 1/59,968 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000929% 15/1,613,902 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,968
African / African-American	0.00134%	74,874
South Asian	0.0011%	91,068
European (non-Finnish)	0.00102%	98,332

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: DDB2
Protein: p.Gly232Ser
Coding: c.694G>A
MANE Select: NM_000107
dbSNP: rs774675310
Type: single nucleotide variant
Location: chr11:47234664 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.69 · 10 PDB
Residue 232: a β-strand

Full DDB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDB2 c.702+1G>T Pathogenic/Likely pathogenic ★★ same type
DDB2 p.Arg192Ter Pathogenic/Likely pathogenic ★★ same type
DDB2 p.Arg273His Pathogenic/Likely pathogenic ★★ ⚠ same type
DDB2 p.Arg355Ter Pathogenic ★★ same type
DDB2 p.Arg332His Uncertain significance ★★ ⚠ same type
DDB2 p.Cys66Gly Uncertain significance ★★ ⚠ same type
DDB2 p.Glu178Ala Uncertain significance ★★ ⚠ same type
DDB2 p.Leu350Pro 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/ddb2-p-gly232ser (accessed [today's date]).

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