Is ABHD11 p.Phe73Val (c.217T>G) pathogenic?

ABHD11 p.Phe73Val (c.217T>G) is classified Uncertain significance in ABHD11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: ambiguous (0.5626); Very rare (popmax 0.00167%, amr).

How common is ABHD11 p.Phe73Val (c.217T>G) in the general population?

ABHD11 p.Phe73Val (c.217T>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ABHD11 p.Phe73Val (c.217T>G)?

AlphaMissense predicts ambiguous (score 0.5626) — an in-silico prediction, not a clinical call.

ABHD11 p.Phe73Val

c.217T>G · VCV4154592

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5626 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
AlphaMissense	0.5626	ambiguous
REVEL	0.707	pathogenic-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 6.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 2,208 bp · p 0.044 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F82V vs ClinVar F73V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,904 alleles

Overall 6.2e-05% 1/1,613,388 alleles · very rare exomes 1/1,461,306 · genomes 0/152,082 · joint denominator

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: ABHD11
Protein: p.Phe73Val
Coding: c.217T>G
MANE Select: NM_148912
Type: single nucleotide variant
Location: chr7:73738372 (GRCh38)
Gene constraint: LOEUF 1.194 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.41

Full ABHD11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD11 c.-18G>T Uncertain significance ★ ⚠ same type
ABHD11 p.Ala154Thr Uncertain significance ★ ⚠ same type
ABHD11 p.Ala181Thr Uncertain significance ★ ⚠ same type
ABHD11 p.Ala193Val Uncertain significance ★ ⚠ same type
ABHD11 p.Ala285Thr Uncertain significance ★ same type
ABHD11 p.Ala7Pro Uncertain significance ★ ⚠ same type
ABHD11 p.Ala81Val Uncertain significance ★ ⚠ same type
ABHD11 p.Arg151Cys 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/abhd11-p-phe73val (accessed [today's date]).

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