Is DUS2 p.Ala36Val (c.107C>T) pathogenic?

DUS2 p.Ala36Val (c.107C>T) is classified Uncertain significance in DUS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-06). AlphaMissense: likely pathogenic (0.7405); Ultra-rare (popmax 0.045%, sas).

How common is DUS2 p.Ala36Val (c.107C>T) in the general population?

DUS2 p.Ala36Val (c.107C>T) is ultra-rare (popmax 0.045%, sas) (gnomAD).

What do computational predictors say about DUS2 p.Ala36Val (c.107C>T)?

AlphaMissense predicts likely pathogenic (score 0.7405) — an in-silico prediction, not a clinical call.

DUS2 p.Ala36Val

c.107C>T · rs375337192 · VCV3086206

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7405 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7405	likely pathogenic
REVEL	0.438	indeterminate
SaProt	LLR -11.95	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 41 kb · p 0.0097 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.045% South Asian · 41/91,048 alleles

Filtering AF 0.0341% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0302%

Overall 0.00353% 57/1,613,592 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.045%	2,221
Remaining individualsnot grpmax-eligible	0.008%	12,498
African / African-American	0.00267%	37,454
European (non-Finnish)	0.000763%	131,090

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.Ala36Val
Coding: c.107C>T
MANE Select: NM_017803
dbSNP: rs375337192
Type: single nucleotide variant
Location: chr16:68038130 (GRCh38)
Gene constraint: LOEUF 0.875 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.81 · 11 PDB
Residue 36: the 'catalytic domain' region

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.Ala271Val Uncertain significance ★ ⚠ same type
DUS2 p.Ala336Thr Uncertain significance ★ ⚠ same type
DUS2 p.Ala346Val 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-ala36val (accessed [today's date]).

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