Is DSE p.Met211Val (c.631A>G) pathogenic?

DSE p.Met211Val (c.631A>G) is classified Uncertain significance in DSE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-09). AlphaMissense: likely benign (0.0586); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with DSE p.Met211Val (c.631A>G)?

DSE p.Met211Val (c.631A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DSE p.Met211Val (c.631A>G) in the general population?

DSE p.Met211Val (c.631A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about DSE p.Met211Val (c.631A>G)?

AlphaMissense predicts likely benign (score 0.0586) — an in-silico prediction, not a clinical call.

DSE p.Met211Val

c.631A>G · VCV3505375

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0586 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0586	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -3.86	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 7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 36 kb · p 6.1e-20 · regional, not allelic
Overall
CADD	15.32	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 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.000186% 3/1,614,176 alleles · ultra-rare exomes 3/1,461,836 · genomes 0/152,340 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)	8.47e-05%	1,180,008

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.Met211Val
Coding: c.631A>G
MANE Select: NM_013352
Type: single nucleotide variant
Location: chr6:116426788 (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 211: 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.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-met211val (accessed [today's date]).

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