Is AGPAT5 p.Ala91Pro (c.271G>C) pathogenic?

AGPAT5 p.Ala91Pro (c.271G>C) is classified Uncertain significance in AGPAT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely pathogenic (0.9401); Absent from gnomAD v4.1.

How common is AGPAT5 p.Ala91Pro (c.271G>C) in the general population?

AGPAT5 p.Ala91Pro (c.271G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGPAT5 p.Ala91Pro (c.271G>C)?

AlphaMissense predicts likely pathogenic (score 0.9401) — an in-silico prediction, not a clinical call.

AGPAT5 p.Ala91Pro

c.271G>C · VCV4639020

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9401 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,170,990)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9401	likely pathogenic
REVEL	0.655	pathogenic-leaning
SaProt	LLR -10.37	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP -1.4, phastCons 1
Regional constraint	o/e 1.49	unconstrained · MANE · 49 kb · p 1.2e-25 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,170,990). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AGPAT5
Protein: p.Ala91Pro
Coding: c.271G>C
MANE Select: NM_018361
Type: single nucleotide variant
Location: chr8:6724921 (GRCh38)
Gene constraint: LOEUF 1.391 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.23

Full AGPAT5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGPAT5 p.His212= Likely benign ★★ same type
AGPAT5 p.Ala102Ser Uncertain significance ★ ⚠ same type
AGPAT5 p.Ala193Ser Uncertain significance ★ ⚠ same type
AGPAT5 p.Ala31Ser Uncertain significance ★ ⚠ same type
AGPAT5 p.Ala31Thr Uncertain significance ★ ⚠ same type
AGPAT5 p.Arg116His Uncertain significance ★ ⚠ same type
AGPAT5 p.Arg13Gly Uncertain significance ★ ⚠ same type
AGPAT5 p.Arg143Cys 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/agpat5-p-ala91pro (accessed [today's date]).

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