Is DSE p.Ile941Val (c.2821A>G) pathogenic?

DSE p.Ile941Val (c.2821A>G) is classified Conflicting classifications of pathogenicity in DSE (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-05-30). AlphaMissense: likely benign (0.064); Rare (popmax 0.165%, mid); Associated with Inborn genetic diseases.

What condition is associated with DSE p.Ile941Val (c.2821A>G)?

DSE p.Ile941Val (c.2821A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DSE p.Ile941Val (c.2821A>G) in the general population?

DSE p.Ile941Val (c.2821A>G) is rare (popmax 0.165%, mid) (gnomAD).

What do computational predictors say about DSE p.Ile941Val (c.2821A>G)?

AlphaMissense predicts likely benign (score 0.064) — an in-silico prediction, not a clinical call.

DSE p.Ile941Val

c.2821A>G · VCV3273829

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.064 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.064	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -6.19	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 0.16	GERP -4.1
Regional constraint	o/e 0.90	unconstrained · MANE · 870 bp · p 0.076 · regional, not allelic
Overall
CADD	5.54	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 0.165% Middle Eastern · 10/6,078 alleles

Filtering AF 0.0892% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0679%

Overall 0.0026% 42/1,613,858 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.165%	608
Admixed American	0.0117%	8,570
Remaining individualsnot grpmax-eligible	0.008%	12,497
South Asian	0.00329%	30,355
European (non-Finnish)	0.00144%	69,409

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.Ile941Val
Coding: c.2821A>G
MANE Select: NM_013352
Type: single nucleotide variant
Location: chr6:116437289 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI 0.06 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.59 · 1 PDB

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.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
DSE p.Arg97His 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-ile941val (accessed [today's date]).

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