Is FAAH2 p.Pro43Ser (c.127C>T) pathogenic?

FAAH2 p.Pro43Ser (c.127C>T) is classified Uncertain significance in FAAH2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.0982); No allele count reported in gnomAD v4.1 (AN 1,203,311); Associated with FAAH2-related disorder.

What condition is associated with FAAH2 p.Pro43Ser (c.127C>T)?

FAAH2 p.Pro43Ser (c.127C>T) is associated with FAAH2-related disorder (ClinVar).

How common is FAAH2 p.Pro43Ser (c.127C>T) in the general population?

FAAH2 p.Pro43Ser (c.127C>T) is no allele count reported in gnomAD v4.1 (AN 1,203,311) (gnomAD).

What do computational predictors say about FAAH2 p.Pro43Ser (c.127C>T)?

AlphaMissense predicts likely benign (score 0.0982) — an in-silico prediction, not a clinical call.

FAAH2 p.Pro43Ser

c.127C>T · rs2051826047 · VCV3033341

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0982 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,203,311)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

FAAH2-related disorder

Computational evidence

Protein change
AlphaMissense	0.0982	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -9.34	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 2	phastCons 0.14
Regional constraint	o/e 1.73	unconstrained · MANE · 202 kb · p 2.2e-48 · regional, not allelic
Overall
CADD	14.48	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

No allele count reported in gnomAD v4.1 (AN 1,203,311). 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: FAAH2
Protein: p.Pro43Ser
Coding: c.127C>T
MANE Select: NM_174912
dbSNP: rs2051826047
Type: single nucleotide variant
Location: chrX:57286952 (GRCh38)
Structure: AlphaFold pLDDT 94.08

Full FAAH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

FAAH2-related disorder

Similar variants

FAAH2 p.Met310Ile Uncertain significance ★ ⚠ same condition
FAAH2 p.Trp309Ter Uncertain significance ★ same condition
FAAH2 p.Trp392Ter Pathogenic same condition
FAAH2 p.Ser230Asn Uncertain significance ⚠ same condition
FAAH2 p.Val300Leu Uncertain significance ⚠ same condition
FAAH2 p.Ala362Thr Likely benign same condition
FAAH2 p.Asn195= Likely benign same condition
FAAH2 p.Glu432Ter Likely benign 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/faah2-p-pro43ser (accessed [today's date]).

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