Is FAAH2 p.Pro468Ser (c.1402C>T) pathogenic?

FAAH2 p.Pro468Ser (c.1402C>T) is classified Uncertain significance in FAAH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-26). AlphaMissense: likely pathogenic (0.6819); Absent from gnomAD v4.1.

How common is FAAH2 p.Pro468Ser (c.1402C>T) in the general population?

FAAH2 p.Pro468Ser (c.1402C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FAAH2 p.Pro468Ser (c.1402C>T)?

AlphaMissense predicts likely pathogenic (score 0.6819) — an in-silico prediction, not a clinical call.

FAAH2 p.Pro468Ser

c.1402C>T · VCV3277010

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6819 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6819	likely pathogenic
REVEL	0.537	indeterminate
SaProt	LLR -11.92	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.62	GERP 0.7, phastCons 0.81
Regional constraint	o/e 1.73	unconstrained · MANE · 202 kb · p 2.2e-48 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FAAH2
Protein: p.Pro468Ser
Coding: c.1402C>T
MANE Select: NM_174912
Type: single nucleotide variant
Location: chrX:57448697 (GRCh38)
Structure: AlphaFold pLDDT 94.08

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

Similar variants

FAAH2 p.Pro468= Benign ★★ same residue
FAAH2 c.1229-14A>T Benign ★★ same type
FAAH2 p.Arg274= Benign ★★ same type
FAAH2 p.Arg42Trp Benign ★★ same type
FAAH2 c.742+5T>A Uncertain significance ★ same type
FAAH2 p.Ala115Val Uncertain significance ★ ⚠ same type
FAAH2 p.Ala157Asp Uncertain significance ★ ⚠ same type
FAAH2 p.Ala161Thr 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/faah2-p-pro468ser (accessed [today's date]).

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