Is ABHD5 p.Pro210Ala (c.628C>G) pathogenic?

ABHD5 p.Pro210Ala (c.628C>G) is classified Uncertain significance in ABHD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-29). AlphaMissense: likely pathogenic (0.8015); Ultra-rare (popmax 0.0914%, eas).

How common is ABHD5 p.Pro210Ala (c.628C>G) in the general population?

ABHD5 p.Pro210Ala (c.628C>G) is ultra-rare (popmax 0.0914%, eas) (gnomAD).

What do computational predictors say about ABHD5 p.Pro210Ala (c.628C>G)?

AlphaMissense predicts likely pathogenic (score 0.8015) — an in-silico prediction, not a clinical call.

ABHD5 p.Pro210Ala

c.628C>G · rs189968197 · VCV1896605

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8015 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0914%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8015	likely pathogenic
REVEL	0.549	indeterminate
SaProt	LLR -11.87	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 28 kb · p 0.24 · regional, not allelic
Overall
CADD	26.3	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

Grpmax group 0.0914% East Asian · 41/44,882 alleles

Filtering AF 0.0692% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0614%

Overall 0.0031% 50/1,614,184 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0914%	1,095
Remaining individualsnot grpmax-eligible	0.0064%	15,627
South Asian	0.00549%	18,216

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: ABHD5
Protein: p.Pro210Ala
Coding: c.628C>G
MANE Select: NM_016006
dbSNP: rs189968197
Type: single nucleotide variant
Location: chr3:43711830 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.62

Full ABHD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD5 c.133+1G>A Likely pathogenic ★★ same type
ABHD5 c.507-1G>A Pathogenic ★★ same type
ABHD5 p.Arg184Ter Pathogenic ★★ same type
ABHD5 p.Arg234Ter Pathogenic ★★ same type
ABHD5 p.Arg280Ter Pathogenic/Likely pathogenic ★★ same type
ABHD5 p.Glu336Ter Pathogenic/Likely pathogenic ★★ same type
ABHD5 p.Arg56His Uncertain significance ★★ ⚠ same type
ABHD5 p.Asp12Asn 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/abhd5-p-pro210ala (accessed [today's date]).

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