Is DAGLB p.Ile643Val (c.1927A>G) pathogenic?

DAGLB p.Ile643Val (c.1927A>G) is classified Likely benign in DAGLB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.0635); Ultra-rare (popmax 0.0312%, nfe).

How common is DAGLB p.Ile643Val (c.1927A>G) in the general population?

DAGLB p.Ile643Val (c.1927A>G) is ultra-rare (popmax 0.0312%, nfe) (gnomAD).

What do computational predictors say about DAGLB p.Ile643Val (c.1927A>G)?

AlphaMissense predicts likely benign (score 0.0635) — an in-silico prediction, not a clinical call.

DAGLB p.Ile643Val

c.1927A>G · rs138127497 · VCV2372216

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0635 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0635	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -4.39	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 -1.2	GERP 0.73
Regional constraint	o/e 1.20	unconstrained · MANE · 38 kb · p 1.4e-09 · regional, not allelic
Overall
CADD	0.014	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 0.0312% European (non-Finnish) · 368/1,180,046 alleles

Filtering AF 0.0285% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0275%

Overall 0.0239% 385/1,614,128 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0312%	3,207
Remaining individualsnot grpmax-eligible	0.016%	6,251
African / African-American	0.00666%	15,007
East Asian	0.00223%	44,874
Admixed American	0.00167%	60,026

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: DAGLB
Protein: p.Ile643Val
Coding: c.1927A>G
MANE Select: NM_139179
dbSNP: rs138127497
Type: single nucleotide variant
Location: chr7:6409929 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.18

Full DAGLB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAGLB p.Asp247Glu Uncertain significance ★★ ⚠ same type
DAGLB p.Asn131= Benign/Likely benign ★★ same type
DAGLB p.Gly632= Benign/Likely benign ★★ same type
DAGLB p.Ala116Thr Uncertain significance ★ ⚠ same type
DAGLB p.Ala12Thr Uncertain significance ★ ⚠ same type
DAGLB p.Ala145Thr Uncertain significance ★ ⚠ same type
DAGLB p.Ala145Val Uncertain significance ★ ⚠ same type
DAGLB p.Ala146Gly Uncertain significance ★ ⚠ same type

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/daglb-p-ile643val (accessed [today's date]).

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