Is DGAT2 p.Ser247Phe (c.740C>T) pathogenic?

DGAT2 p.Ser247Phe (c.740C>T) is classified Uncertain significance in DGAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-24). AlphaMissense: likely pathogenic (0.8248); Very rare (popmax 0.000258%, nfe).

How common is DGAT2 p.Ser247Phe (c.740C>T) in the general population?

DGAT2 p.Ser247Phe (c.740C>T) is very rare (popmax 0.000258%, nfe) (gnomAD).

What do computational predictors say about DGAT2 p.Ser247Phe (c.740C>T)?

AlphaMissense predicts likely pathogenic (score 0.8248) — an in-silico prediction, not a clinical call.

DGAT2 p.Ser247Phe

c.740C>T · VCV4659682

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8248 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000258%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8248	likely pathogenic
REVEL	0.224	benign-leaning
SaProt	LLR -9.23	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.96, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 32 kb · p 0.032 · regional, not allelic
Overall
CADD	26.6	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 0.000258% European (non-Finnish) · 3/1,162,628 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00021% 3/1,426,466 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: DGAT2
Protein: p.Ser247Phe
Coding: c.740C>T
MANE Select: NM_032564
Type: single nucleotide variant
Location: chr11:75797263 (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-ser247phe (accessed [today's date]).

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