Is ABHD17C p.Pro73Ser (c.217C>T) pathogenic?

ABHD17C p.Pro73Ser (c.217C>T) is classified Uncertain significance in ABHD17C (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-28). AlphaMissense: likely benign (0.065); Ultra-rare (popmax 0.0388%, sas).

How common is ABHD17C p.Pro73Ser (c.217C>T) in the general population?

ABHD17C p.Pro73Ser (c.217C>T) is ultra-rare (popmax 0.0388%, sas) (gnomAD).

What do computational predictors say about ABHD17C p.Pro73Ser (c.217C>T)?

AlphaMissense predicts likely benign (score 0.065) — an in-silico prediction, not a clinical call.

ABHD17C p.Pro73Ser

c.217C>T · VCV3428652

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.065 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0388%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.065	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -7.52	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 0.79	GERP -1.4, phastCons 0.3
Regional constraint	o/e 0.52	unconstrained · MANE · 59 kb · p 2.1e-21 · regional, not allelic
Overall
CADD	15.23	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 0.0388% South Asian · 22/56,744 alleles

Filtering AF 0.0262% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.00177% 24/1,354,806 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0388%	2,579
African / African-American	0.00155%	64,684
European (non-Finnish)	9.42e-05%	1,062,080

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: ABHD17C
Protein: p.Pro73Ser
Coding: c.217C>T
MANE Select: NM_021214
Type: single nucleotide variant
Location: chr15:80695646 (GRCh38)
Gene constraint: LOEUF 0.919 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.94
Residue 73: the 'disordered' region

Full ABHD17C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD17C p.Ala115Val Uncertain significance ★ ⚠ same type
ABHD17C p.Ala185Ser Uncertain significance ★ ⚠ same type
ABHD17C p.Ala193Glu Uncertain significance ★ ⚠ same type
ABHD17C p.Ala54Thr Uncertain significance ★ ⚠ same type
ABHD17C p.Ala60Val Uncertain significance ★ ⚠ same type
ABHD17C p.Ala62Gly Uncertain significance ★ ⚠ same type
ABHD17C p.Ala86Val Uncertain significance ★ ⚠ same type
ABHD17C p.Arg119Pro 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/abhd17c-p-pro73ser (accessed [today's date]).

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