Is ABHD18 p.Ala136Asp (c.407C>A) pathogenic?

ABHD18 p.Ala136Asp (c.407C>A) is classified Uncertain significance in ABHD18 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: ambiguous (0.526); Absent from gnomAD v4.1.

How common is ABHD18 p.Ala136Asp (c.407C>A) in the general population?

ABHD18 p.Ala136Asp (c.407C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABHD18 p.Ala136Asp (c.407C>A)?

AlphaMissense predicts ambiguous (score 0.526) — an in-silico prediction, not a clinical call.

ABHD18 p.Ala136Asp

c.407C>A · rs2546457938 · VCV3130904

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.526 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,523,538)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.526	ambiguous
REVEL	0.722	pathogenic-leaning
SaProt	LLR -6.68	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 38 kb · p 0.8 · regional, not allelic
Overall
CADD	32.0	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

No allele count reported in gnomAD v4.1 (AN 1,523,538). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABHD18
Protein: p.Ala136Asp
Coding: c.407C>A
MANE Select: NM_001358451
dbSNP: rs2546457938
Type: single nucleotide variant
Location: chr4:128009156 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.82

Full ABHD18 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MFSD8 c.-100G>C Benign ★★ same type
MFSD8 c.-75-215A>G Benign ★★ same type
MFSD8 c.-75-333C>G Benign ★★ same type
ABHD18 p.Ala439Thr Uncertain significance ★ ⚠ same type
ABHD18 p.Ala78Thr Uncertain significance ★ ⚠ same type
ABHD18 p.Arg11Gln Uncertain significance ★ ⚠ same type
ABHD18 p.Arg11Trp Uncertain significance ★ ⚠ same type
ABHD18 p.Arg124Gly 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/abhd18-p-ala136asp (accessed [today's date]).

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