Is DSE p.Asp438His (c.1312G>C) pathogenic?

DSE p.Asp438His (c.1312G>C) is classified Uncertain significance in DSE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-31). AlphaMissense: likely benign (0.2555); Ultra-rare (popmax 0.0245%, eas); Associated with Inborn genetic diseases.

What condition is associated with DSE p.Asp438His (c.1312G>C)?

DSE p.Asp438His (c.1312G>C) is associated with Inborn genetic diseases (ClinVar).

How common is DSE p.Asp438His (c.1312G>C) in the general population?

DSE p.Asp438His (c.1312G>C) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

What do computational predictors say about DSE p.Asp438His (c.1312G>C)?

AlphaMissense predicts likely benign (score 0.2555) — an in-silico prediction, not a clinical call.

DSE p.Asp438His

c.1312G>C · rs768202990 · VCV3085916

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2555 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2555	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -6.53	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 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 36 kb · p 6.1e-20 · 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 0.0245% East Asian · 11/44,896 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.000743% 12/1,614,006 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,081
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Asp438His
Coding: c.1312G>C
MANE Select: NM_013352
dbSNP: rs768202990
Type: single nucleotide variant
Location: chr6:116435780 (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 438: a turn

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-asp438his (accessed [today's date]).

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