Is DGAT2 p.Ser33Pro (c.97T>C) pathogenic?

DGAT2 p.Ser33Pro (c.97T>C) is classified Uncertain significance in DGAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-26). AlphaMissense: likely benign (0.0665); Very rare (popmax 0.00653%, nfe).

How common is DGAT2 p.Ser33Pro (c.97T>C) in the general population?

DGAT2 p.Ser33Pro (c.97T>C) is very rare (popmax 0.00653%, nfe) (gnomAD).

What do computational predictors say about DGAT2 p.Ser33Pro (c.97T>C)?

AlphaMissense predicts likely benign (score 0.0665) — an in-silico prediction, not a clinical call.

DGAT2 p.Ser33Pro

c.97T>C · rs555522864 · VCV2222732

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0665 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00653%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0665	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -6.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.4	GERP -2.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 32 kb · p 0.032 · regional, not allelic
Overall
CADD	13.71	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 0.00653% European (non-Finnish) · 76/1,163,802 alleles

Filtering AF 0.00535% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00488%

Overall 0.00509% 80/1,572,554 alleles · very rare exomes 70/1,420,362 · genomes 10/152,192 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00653%	15,313
African / African-American	0.0028%	35,773
Finnishnot grpmax-eligible	0.00167%	60,014
Remaining individualsnot grpmax-eligible	0.00164%	60,914

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.Ser33Pro
Coding: c.97T>C
MANE Select: NM_032564
dbSNP: rs555522864
Type: single nucleotide variant
Location: chr11:75769088 (GRCh38)
Gene constraint: LOEUF 0.93 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.52
Residue 33: the 'disordered' region

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-ser33pro (accessed [today's date]).

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