Is DGAT1 p.Pro238Ser (c.712C>T) pathogenic?

DGAT1 p.Pro238Ser (c.712C>T) is classified Uncertain significance in DGAT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-11). AlphaMissense: likely benign (0.0674); Very rare (popmax 0.00191%, amr); Associated with Inborn genetic diseases.

What condition is associated with DGAT1 p.Pro238Ser (c.712C>T)?

DGAT1 p.Pro238Ser (c.712C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DGAT1 p.Pro238Ser (c.712C>T) in the general population?

DGAT1 p.Pro238Ser (c.712C>T) is very rare (popmax 0.00191%, amr) (gnomAD).

What do computational predictors say about DGAT1 p.Pro238Ser (c.712C>T)?

AlphaMissense predicts likely benign (score 0.0674) — an in-silico prediction, not a clinical call.

DGAT1 p.Pro238Ser

c.712C>T · rs1554847514 · VCV1357460

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0674 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00191%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0674	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -5.69	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 4.8	GERP 0.65, phastCons 0.94
Regional constraint	o/e 0.88	unconstrained · MANE · 10 kb · p 0.0026 · regional, not allelic
Overall
CADD	5.758	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 0.00191% Admixed American · 1/52,274 alleles

Filtering AF 0.000439% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00032%

Overall 0.000781% 11/1,408,374 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00191%	52,274
European (non-Finnish)	0.000868%	115,255

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: DGAT1
Protein: p.Pro238Ser
Coding: c.712C>T
MANE Select: NM_012079
dbSNP: rs1554847514
Type: single nucleotide variant
Location: chr8:144318134 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.86 · 5 PDB
Residue 238: the 'mboat fold' region; the 'intracellular loop 1 (il1)' region

Full DGAT1 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

DGAT1 p.Pro238= Likely benign ★★ same residue
DGAT1 p.Pro238Leu Uncertain significance ★ ⚠ same residue
DGAT1 p.Ala144Pro Uncertain significance ★★ ⚠ same condition
DGAT1 p.Ala221Gly Uncertain significance ★★ ⚠ same condition
DGAT1 p.Ala221Thr Uncertain significance ★★ ⚠ same condition
DGAT1 p.Arg250Leu Uncertain significance ★★ ⚠ same condition
DGAT1 p.Arg32Leu Uncertain significance ★★ ⚠ same condition
DGAT1 p.Glu321Lys 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/dgat1-p-pro238ser (accessed [today's date]).

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