Is DGAT2 p.Asn149Ser (c.446A>G) pathogenic?

DGAT2 p.Asn149Ser (c.446A>G) is classified Uncertain significance in DGAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-10). AlphaMissense: likely benign (0.0771); Very rare (popmax 0.00223%, eas).

How common is DGAT2 p.Asn149Ser (c.446A>G) in the general population?

DGAT2 p.Asn149Ser (c.446A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DGAT2 p.Asn149Ser (c.446A>G)?

AlphaMissense predicts likely benign (score 0.0771) — an in-silico prediction, not a clinical call.

DGAT2 p.Asn149Ser

c.446A>G · VCV3839590

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0771 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0771	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -7.11	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 11	GERP 2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 32 kb · p 0.032 · regional, not allelic
Overall
CADD	21.7	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 0.00223% East Asian · 1/44,866 alleles

Overall 0.000137% 2/1,461,722 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,866
European (non-Finnish)	8.48e-05%	1,179,908

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: DGAT2
Protein: p.Asn149Ser
Coding: c.446A>G
MANE Select: NM_032564
Type: single nucleotide variant
Location: chr11:75796344 (GRCh38)
Gene constraint: LOEUF 0.93 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.52

Full DGAT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DGAT2 p.Glu15Val Uncertain significance ★★ ⚠ same type
DGAT2 p.Ile313Val Uncertain significance ★★ ⚠ same type
DGAT2 p.Tyr223Ser Uncertain significance ★★ ⚠ same type
DGAT2 p.Arg297Gln Benign/Likely benign ★★ ⚠ same type
DGAT2 p.Gly318Ser Likely benign ★★ ⚠ same type
DGAT2 p.Ile355= Likely benign ★★ same type
DGAT2 p.Ser230= Benign/Likely benign ★★ same type
DGAT2 p.Ala253Val 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/dgat2-p-asn149ser (accessed [today's date]).

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