Is DAGLA p.Ser761Phe (c.2282C>T) pathogenic?

DAGLA p.Ser761Phe (c.2282C>T) is classified Uncertain significance in DAGLA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-12). AlphaMissense: ambiguous (0.4329); Very rare (popmax 6.91e-05%); Associated with Inborn genetic diseases.

What condition is associated with DAGLA p.Ser761Phe (c.2282C>T)?

DAGLA p.Ser761Phe (c.2282C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DAGLA p.Ser761Phe (c.2282C>T) in the general population?

DAGLA p.Ser761Phe (c.2282C>T) is very rare (popmax 6.91e-05%) (gnomAD).

What do computational predictors say about DAGLA p.Ser761Phe (c.2282C>T)?

AlphaMissense predicts ambiguous (score 0.4329) — an in-silico prediction, not a clinical call.

DAGLA p.Ser761Phe

c.2282C>T · rs2540756148 · VCV2328358

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4329 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.91e-05%)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4329	ambiguous
REVEL	0.061	moderately benign-leaning
SaProt	LLR -10.23	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 3,256 bp · p 0.002 · regional, not allelic
Overall
CADD	26.2	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 6.91e-05%

Overall 6.91e-05% 1/1,447,364 alleles · very rare

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: DAGLA
Protein: p.Ser761Phe
Coding: c.2282C>T
MANE Select: NM_006133
dbSNP: rs2540756148
Type: single nucleotide variant
Location: chr11:61743642 (GRCh38)
Gene constraint: LOEUF 0.305 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87

Full DAGLA 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

DAGLA p.Ile823Thr Uncertain significance ★★ ⚠ same condition
DAGLA p.Val117Ile Likely benign ★★ same condition
DAGLA p.Ala253Thr Uncertain significance ★ ⚠ same condition
DAGLA p.Ala336Thr Uncertain significance ★ ⚠ same condition
DAGLA p.Ala351Thr Uncertain significance ★ ⚠ same condition
DAGLA p.Ala518Ser Uncertain significance ★ ⚠ same condition
DAGLA p.Ala614Ser Uncertain significance ★ ⚠ same condition
DAGLA p.Ala716Val 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/dagla-p-ser761phe (accessed [today's date]).

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