Is DUS2 p.Ala271Val (c.812C>T) pathogenic?

DUS2 p.Ala271Val (c.812C>T) is classified Uncertain significance in DUS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). AlphaMissense: likely pathogenic (0.6931); Ultra-rare (popmax 0.0459%, nfe).

How common is DUS2 p.Ala271Val (c.812C>T) in the general population?

DUS2 p.Ala271Val (c.812C>T) is ultra-rare (popmax 0.0459%, nfe) (gnomAD).

What do computational predictors say about DUS2 p.Ala271Val (c.812C>T)?

AlphaMissense predicts likely pathogenic (score 0.6931) — an in-silico prediction, not a clinical call.

DUS2 p.Ala271Val

c.812C>T · rs138485465 · VCV2344064

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6931 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0459%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6931	likely pathogenic
REVEL	0.223	benign-leaning
SaProt	LLR -8.79	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 41 kb · p 0.0097 · regional, not allelic
Overall
CADD	32.0	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 0.0459% European (non-Finnish) · 541/1,179,888 alleles

Filtering AF 0.0426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0414%

Overall 0.034% 548/1,613,972 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0459%	2,181
Remaining individualsnot grpmax-eligible	0.0096%	10,415
Admixed American	0.00167%	60,022

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: DUS2
Protein: p.Ala271Val
Coding: c.812C>T
MANE Select: NM_017803
dbSNP: rs138485465
Type: single nucleotide variant
Location: chr16:68074035 (GRCh38)
Gene constraint: LOEUF 0.875 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.81 · 11 PDB
Residue 271: the 'catalytic domain' region; an α-helix

Full DUS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUS2 p.Ala181Thr Uncertain significance ★ ⚠ same type
DUS2 p.Ala244Gly Uncertain significance ★ ⚠ same type
DUS2 p.Ala336Thr Uncertain significance ★ ⚠ same type
DUS2 p.Ala346Val Uncertain significance ★ ⚠ same type
DUS2 p.Ala36Val Uncertain significance ★ ⚠ same type
DUS2 p.Ala425Val Uncertain significance ★ ⚠ same type
DUS2 p.Arg101Thr Uncertain significance ★ ⚠ same type
DUS2 p.Arg149Pro 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/dus2-p-ala271val (accessed [today's date]).

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