Is DDIAS p.Cys490Ser (c.1468T>A) pathogenic?

DDIAS p.Cys490Ser (c.1468T>A) is classified Likely benign in DDIAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.0651); Very rare (popmax 0.0022%, sas).

How common is DDIAS p.Cys490Ser (c.1468T>A) in the general population?

DDIAS p.Cys490Ser (c.1468T>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about DDIAS p.Cys490Ser (c.1468T>A)?

AlphaMissense predicts likely benign (score 0.0651) — an in-silico prediction, not a clinical call.

DDIAS p.Cys490Ser

c.1468T>A · rs1861027523 · VCV3080745

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0651 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0651	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -4.87	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 1.1	GERP 0.65, phastCons 0.79
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.0043 · regional, not allelic
Overall
CADD	2.442	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 0.0022% South Asian · 2/91,078 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000205% 3/1,461,410 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,539
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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.Cys490Ser
Coding: c.1468T>A
MANE Select: NM_145018
dbSNP: rs1861027523
Type: single nucleotide variant
Location: chr11:82932806 (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-cys490ser (accessed [today's date]).

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