Is DUS2 p.Ser295Leu (c.884C>T) pathogenic?

DUS2 p.Ser295Leu (c.884C>T) is classified Uncertain significance in DUS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely benign (0.1934); Very rare (popmax 0.004%, afr).

How common is DUS2 p.Ser295Leu (c.884C>T) in the general population?

DUS2 p.Ser295Leu (c.884C>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about DUS2 p.Ser295Leu (c.884C>T)?

AlphaMissense predicts likely benign (score 0.1934) — an in-silico prediction, not a clinical call.

DUS2 p.Ser295Leu

c.884C>T · rs779701580 · VCV2469971

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1934 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1934	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -8.73	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 6	phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 41 kb · p 0.0097 · regional, not allelic
Overall
CADD	25.9	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 0.004% African / African-American · 3/74,930 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.0013% 21/1,614,060 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
African / African-Americangrpmax	0.004%	24,977
Remaining individualsnot grpmax-eligible	0.0032%	31,241
European (non-Finnish)	0.0011%	90,771

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser295Leu
Coding: c.884C>T
MANE Select: NM_017803
dbSNP: rs779701580
Type: single nucleotide variant
Location: chr16:68074107 (GRCh38)
Gene constraint: LOEUF 0.875 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.81 · 11 PDB
Residue 295: 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.Ala36Val Uncertain significance ★ ⚠ same type
DUS2 p.Ala425Val Uncertain significance ★ same type
DUS2 p.Arg101Thr 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-ser295leu (accessed [today's date]).

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