Is DCUN1D3 p.Arg90Ser (c.270A>T) pathogenic?

DCUN1D3 p.Arg90Ser (c.270A>T) is classified Uncertain significance in DCUN1D3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: ambiguous (0.3427); Ultra-rare (popmax 0.0999%, afr).

How common is DCUN1D3 p.Arg90Ser (c.270A>T) in the general population?

DCUN1D3 p.Arg90Ser (c.270A>T) is ultra-rare (popmax 0.0999%, afr) (gnomAD).

What do computational predictors say about DCUN1D3 p.Arg90Ser (c.270A>T)?

AlphaMissense predicts ambiguous (score 0.3427) — an in-silico prediction, not a clinical call.

DCUN1D3 p.Arg90Ser

c.270A>T · VCV4238312

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3427 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0999%, afr)

Computational evidence

Protein change
AlphaMissense	0.3427	ambiguous
REVEL	0.573	indeterminate
SaProt	LLR -7.85	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.33	GERP -3.8, phastCons 0.001
Regional constraint	o/e 0.68	unconstrained · MANE · 2,649 bp · p 4.6e-10 · regional, not allelic
Overall
CADD	18.29	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 0.0999% African / African-American · 75/75,046 alleles

Filtering AF 0.0817% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.075%

Overall 0.00527% 85/1,614,184 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0999%	1,001
Admixed American	0.00833%	12,006
Remaining individualsnot grpmax-eligible	0.0064%	15,628
South Asian	0.0011%	91,078

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: DCUN1D3
Protein: p.Arg90Ser
Coding: c.270A>T
MANE Select: NM_173475
Type: single nucleotide variant
Location: chr16:20862269 (GRCh38)
Gene constraint: LOEUF 0.46 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 80.97 · 1 PDB
Residue 90: an α-helix; the dcun1 domain

Full DCUN1D3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCUN1D3 p.Ala65Asp Uncertain significance ★ ⚠ same type
DCUN1D3 p.Arg102Gln Uncertain significance ★ ⚠ same type
DCUN1D3 p.Arg165Gln Uncertain significance ★ ⚠ same type
DCUN1D3 p.Arg184Gln Uncertain significance ★ ⚠ same type
DCUN1D3 p.Arg22His Uncertain significance ★ ⚠ same type
DCUN1D3 p.Arg240Trp Uncertain significance ★ ⚠ same type
DCUN1D3 p.Arg283Thr Uncertain significance ★ ⚠ same type
DCUN1D3 p.Arg288Gly 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/dcun1d3-p-arg90ser (accessed [today's date]).

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