Is DDAH2 p.Pro4Arg (c.11C>G) pathogenic?

DDAH2 p.Pro4Arg (c.11C>G) is classified Benign in DDAH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-24). AlphaMissense: likely benign (0.0878); Low-frequency (popmax 3.97%, afr).

How common is DDAH2 p.Pro4Arg (c.11C>G) in the general population?

DDAH2 p.Pro4Arg (c.11C>G) is low-frequency (popmax 3.97%, afr) (gnomAD).

What do computational predictors say about DDAH2 p.Pro4Arg (c.11C>G)?

AlphaMissense predicts likely benign (score 0.0878) — an in-silico prediction, not a clinical call.

DDAH2 p.Pro4Arg

c.11C>G · rs73728976 · VCV786084

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0878 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.97%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0878	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -6.99	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 6.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 1,921 bp · p 4.8e-07 · regional, not allelic
Overall
CADD	23.8	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 3.97% African / African-American · 2,963/74,660 alleles

Filtering AF 3.85% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.8%

Overall 0.219% 3,522/1,606,010 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.97%	25
Admixed American	0.409%	245
Remaining individualsnot grpmax-eligible	0.328%	305
Middle Eastern	0.232%	431
South Asian	0.0319%	3,131
European (non-Finnish)	0.00579%	17,282

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: DDAH2
Protein: p.Pro4Arg
Coding: c.11C>G
MANE Select: NM_001303007
dbSNP: rs73728976
Type: single nucleotide variant
Location: chr6:31729151 (GRCh38)
Gene constraint: LOEUF 0.554 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 93.30

Full DDAH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDAH2 p.Ala270Thr Uncertain significance ★ ⚠ same type
DDAH2 p.Arg237Cys Uncertain significance ★ ⚠ same type
DDAH2 p.Asp84Val Uncertain significance ★ ⚠ same type
DDAH2 p.Gly269Val Uncertain significance ★ ⚠ same type
DDAH2 p.Gly26Arg Uncertain significance ★ ⚠ same type
DDAH2 p.His205Arg Uncertain significance ★ ⚠ same type
DDAH2 p.Leu242Pro Uncertain significance ★ ⚠ same type
DDAH2 p.Met178Leu 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/ddah2-p-pro4arg (accessed [today's date]).

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