Is ABHD15 p.Ala358Pro (c.1072G>C) pathogenic?

ABHD15 p.Ala358Pro (c.1072G>C) is classified Uncertain significance in ABHD15 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-03). AlphaMissense: ambiguous (0.4344); Ultra-rare (popmax 0.0493%, mid).

How common is ABHD15 p.Ala358Pro (c.1072G>C) in the general population?

ABHD15 p.Ala358Pro (c.1072G>C) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about ABHD15 p.Ala358Pro (c.1072G>C)?

AlphaMissense predicts ambiguous (score 0.4344) — an in-silico prediction, not a clinical call.

ABHD15 p.Ala358Pro

c.1072G>C · rs757668562 · VCV3130506

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4344 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4344	ambiguous
REVEL	0.177	moderately benign-leaning
SaProt	LLR -12.37	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.49	GERP 0.75
Regional constraint	o/e 0.99	unconstrained · MANE · 4,402 bp · p 0.8 · regional, not allelic
Overall
CADD	16.15	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 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.000496% 8/1,614,048 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
Remaining individualsnot grpmax-eligible	0.008%	12,497

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: ABHD15
Protein: p.Ala358Pro
Coding: c.1072G>C
MANE Select: NM_198147
dbSNP: rs757668562
Type: single nucleotide variant
Location: chr17:29562896 (GRCh38)
Gene constraint: LOEUF 1.479 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.70

Full ABHD15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD15 p.Ala16Pro Uncertain significance ★ ⚠ same type
ABHD15 p.Ala228Val Uncertain significance ★ ⚠ same type
ABHD15 p.Ala229Thr Uncertain significance ★ ⚠ same type
ABHD15 p.Ala233Thr Uncertain significance ★ ⚠ same type
ABHD15 p.Ala260Thr Uncertain significance ★ ⚠ same type
ABHD15 p.Ala291Thr Uncertain significance ★ ⚠ same type
ABHD15 p.Ala444Ser Uncertain significance ★ ⚠ same type
ABHD15 p.Ala6Val 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/abhd15-p-ala358pro (accessed [today's date]).

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