Is DSE p.Val327Ala (c.980T>C) pathogenic?

DSE p.Val327Ala (c.980T>C) is classified Uncertain significance in DSE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). AlphaMissense: ambiguous (0.4133); Ultra-rare (popmax 0.0833%, afr); Associated with Inborn genetic diseases.

What condition is associated with DSE p.Val327Ala (c.980T>C)?

DSE p.Val327Ala (c.980T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DSE p.Val327Ala (c.980T>C) in the general population?

DSE p.Val327Ala (c.980T>C) is ultra-rare (popmax 0.0833%, afr) (gnomAD).

What do computational predictors say about DSE p.Val327Ala (c.980T>C)?

AlphaMissense predicts ambiguous (score 0.4133) — an in-silico prediction, not a clinical call.

DSE p.Val327Ala

c.980T>C · VCV3505370

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4133 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0833%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4133	ambiguous
REVEL	0.315	indeterminate
SaProt	LLR -10.39	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 36 kb · p 6.1e-20 · regional, not allelic
Overall
CADD	24.4	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 0.0833% African / African-American · 61/73,198 alleles

Filtering AF 0.0666% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0605%

Overall 0.00419% 65/1,551,768 alleles · ultra-rare exomes 29/1,399,402 · genomes 36/152,366 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0833%	1,200
Middle Eastern	0.0167%	5,990
Admixed American	0.00392%	25,504
Remaining individualsnot grpmax-eligible	0.00166%	60,116

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: DSE
Protein: p.Val327Ala
Coding: c.980T>C
MANE Select: NM_013352
Type: single nucleotide variant
Location: chr6:116433412 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI 0.06 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.59 · 1 PDB
Residue 327: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DSE p.Val327= Likely benign ★ same residue
DSE p.Ala135Val Uncertain significance ★★ ⚠ same condition
DSE p.Ala584Val Uncertain significance ★★ ⚠ same condition
DSE p.Ala695Thr Uncertain significance ★★ ⚠ same condition
DSE p.Ala910Gly Uncertain significance ★★ ⚠ same condition
DSE p.Arg2Lys Uncertain significance ★★ ⚠ same condition
DSE p.Arg765Gln Uncertain significance ★★ ⚠ same condition
DSE p.Arg815Cys Uncertain significance ★★ ⚠ same condition

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/dse-p-val327ala (accessed [today's date]).

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