Is ABHD16A p.Pro175Ser (c.523C>T) pathogenic?

ABHD16A p.Pro175Ser (c.523C>T) is classified Uncertain significance in ABHD16A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely benign (0.07); Very rare (popmax 0.000248%); Associated with Inborn genetic diseases.

What condition is associated with ABHD16A p.Pro175Ser (c.523C>T)?

ABHD16A p.Pro175Ser (c.523C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABHD16A p.Pro175Ser (c.523C>T) in the general population?

ABHD16A p.Pro175Ser (c.523C>T) is very rare (popmax 0.000248%) (gnomAD).

What do computational predictors say about ABHD16A p.Pro175Ser (c.523C>T)?

AlphaMissense predicts likely benign (score 0.07) — an in-silico prediction, not a clinical call.

ABHD16A p.Pro175Ser

c.523C>T · rs370951628 · VCV2491093

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.07 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000248%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.07	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -5.14	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 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 9,779 bp · p 1.1e-10 · regional, not allelic
Overall
CADD	18.89	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 0.000248%

Overall 0.000248% 4/1,613,672 alleles · very rare

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: ABHD16A
Protein: p.Pro175Ser
Coding: c.523C>T
MANE Select: NM_021160
dbSNP: rs370951628
Type: single nucleotide variant
Location: chr6:31693130 (GRCh38)
Gene constraint: LOEUF 0.686 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.90
Residue 175: a UniProt-annotated variant site (in spg86; no protein detected in homozygous patient cells; increased levels of phosphatidylserine and decreased levels of lysophosphatidylserine in homozygous patient cells, indicating loss of function in phosphatidylserine catabolism)

Full ABHD16A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABHD16A p.Tyr87Cys Uncertain significance ★★ ⚠ same condition
ABHD16A p.Val8Ile Uncertain significance ★★ ⚠ same condition
ABHD16A c.1448-4C>G Uncertain significance ★ same condition
ABHD16A p.Ala412Thr Uncertain significance ★ ⚠ same condition
ABHD16A p.Ala412Val Uncertain significance ★ ⚠ same condition
ABHD16A p.Ala541Asp Uncertain significance ★ ⚠ same condition
ABHD16A p.Ala78Val Uncertain significance ★ ⚠ same condition
ABHD16A p.Arg118Cys Uncertain significance ★ ⚠ same condition

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/abhd16a-p-pro175ser (accessed [today's date]).

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