Is DDIAS p.Ser584Pro (c.1750T>C) pathogenic?

DDIAS p.Ser584Pro (c.1750T>C) is classified Uncertain significance in DDIAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely benign (0.0789); Very rare (popmax 0.00669%, eas).

How common is DDIAS p.Ser584Pro (c.1750T>C) in the general population?

DDIAS p.Ser584Pro (c.1750T>C) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about DDIAS p.Ser584Pro (c.1750T>C)?

AlphaMissense predicts likely benign (score 0.0789) — an in-silico prediction, not a clinical call.

DDIAS p.Ser584Pro

c.1750T>C · VCV3500276

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0789 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0789	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -6.68	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 0.57	GERP 0.7
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.0043 · regional, not allelic
Overall
CADD	10.07	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 0.00669% East Asian · 3/44,820 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00125% 20/1,602,656 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,940
African / African-American	0.00536%	18,669
South Asian	0.00444%	22,527
Admixed American	0.00337%	29,690
Remaining individualsnot grpmax-eligible	0.00321%	31,129
European (non-Finnish)	0.000424%	235,713

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: DDIAS
Protein: p.Ser584Pro
Coding: c.1750T>C
MANE Select: NM_145018
Type: single nucleotide variant
Location: chr11:82933088 (GRCh38)
Gene constraint: LOEUF 1.118 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 43.31

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

Similar variants

DDIAS p.Ala14Thr Uncertain significance ★ ⚠ same type
DDIAS p.Ala260Val Uncertain significance ★ ⚠ same type
DDIAS p.Ala389Ser Uncertain significance ★ ⚠ same type
DDIAS p.Ala402Val Uncertain significance ★ ⚠ same type
DDIAS p.Ala438Gly Uncertain significance ★ ⚠ same type
DDIAS p.Ala478Asp Uncertain significance ★ ⚠ same type
DDIAS p.Ala675Gly Uncertain significance ★ ⚠ same type
DDIAS p.Ala927Val 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/ddias-p-ser584pro (accessed [today's date]).

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