Is CDA p.Gly39Ala (c.116G>C) pathogenic?

CDA p.Gly39Ala (c.116G>C) is classified Uncertain significance in CDA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-17). AlphaMissense: likely pathogenic (0.678); Ultra-rare (popmax 0.0111%, eas).

How common is CDA p.Gly39Ala (c.116G>C) in the general population?

CDA p.Gly39Ala (c.116G>C) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about CDA p.Gly39Ala (c.116G>C)?

AlphaMissense predicts likely pathogenic (score 0.678) — an in-silico prediction, not a clinical call.

CDA p.Gly39Ala

c.116G>C · rs202011087 · VCV3140732

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.678 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.678	likely pathogenic
REVEL	0.649	pathogenic-leaning
SaProt	LLR -13.41	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 29 kb · p 0.079 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0111% East Asian · 5/44,882 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00031% 5/1,613,890 alleles · ultra-rare

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: CDA
Protein: p.Gly39Ala
Coding: c.116G>C
MANE Select: NM_001785
dbSNP: rs202011087
Type: single nucleotide variant
Location: chr1:20589245 (GRCh38)
Gene constraint: LOEUF 0.955 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 94.06 · 1 PDB
Residue 39: the cmp/dcmp-type deaminase domain; a β-strand

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

Similar variants

CDA p.Pro61= Benign ★★ same type
CDA p.Gln92His Uncertain significance ★ ⚠ same type
CDA p.Ile87Leu Uncertain significance ★ ⚠ same type
CDA p.Ile96Val Uncertain significance ★ ⚠ same type
CDA p.Met117Ile Uncertain significance ★ ⚠ same type
CDA p.Pro120Leu Uncertain significance ★ ⚠ same type
CDA p.Thr123Met Uncertain significance ★ ⚠ same type
CDA p.Thr128Met 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/cda-p-gly39ala (accessed [today's date]).

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