Is DAGLA p.Arg892Cys (c.2674C>T) pathogenic?

DAGLA p.Arg892Cys (c.2674C>T) is classified Uncertain significance in DAGLA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-18). AlphaMissense: likely benign (0.0952); Ultra-rare (popmax 0.035%, amr); Associated with Inborn genetic diseases.

What condition is associated with DAGLA p.Arg892Cys (c.2674C>T)?

DAGLA p.Arg892Cys (c.2674C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DAGLA p.Arg892Cys (c.2674C>T) in the general population?

DAGLA p.Arg892Cys (c.2674C>T) is ultra-rare (popmax 0.035%, amr) (gnomAD).

What do computational predictors say about DAGLA p.Arg892Cys (c.2674C>T)?

AlphaMissense predicts likely benign (score 0.0952) — an in-silico prediction, not a clinical call.

DAGLA p.Arg892Cys

c.2674C>T · rs771641156 · VCV3080004

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0952 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0952	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -7.54	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 0.081	GERP -0.98
Regional constraint	o/e 0.86	unconstrained · MANE · 3,256 bp · p 0.002 · regional, not allelic
Overall
CADD	7.119	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 0.035% Admixed American · 21/59,980 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00385% 62/1,612,184 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.035%	2,856
European (non-Finnish)	0.00322%	31,047
South Asian	0.0022%	45,534
African / African-American	0.00134%	74,906

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.Arg892Cys
Coding: c.2674C>T
MANE Select: NM_006133
dbSNP: rs771641156
Type: single nucleotide variant
Location: chr11:61744034 (GRCh38)
Gene constraint: LOEUF 0.305 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87
Residue 892: the 'disordered' region; a UniProt-annotated variant site (in noc2; likely pathogenic); a UniProt-annotated variant site (in noc2; likely pathogenic; may affect subcellular location, leading to the formation of perinuclear aggregates; does not affect protein expression, nor enzymatic activity in vitro); a UniProt-annotated variant site (in noc2; pathogenic)

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-arg892cys (accessed [today's date]).

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