Is FAAH2 p.Pro468= (c.1404T>C) pathogenic?

FAAH2 p.Pro468= (c.1404T>C) is classified Benign in FAAH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2013-08-12). Common (popmax 76.4%, nfe) — too common for a highly-penetrant pathogenic allele.

FAAH2 p.Pro468=

Q: How common is FAAH2 p.Pro468= (c.1404T>C) in the general population?

FAAH2 p.Pro468= (c.1404T>C) is common (popmax 76.4%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1404T>C · rs1367830 · VCV96551

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 76.4%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.4	GERP 0.7, phastCons 1
Overall
CADD	9.283	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 76.4% European (non-Finnish) · 682,912/893,979 alleles

Filtering AF 76.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 76.2%

Overall 70.8% 854,552/1,207,169 alleles · common exomes 794,774/1,096,440 · genomes 59,778/110,729 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	90.1%	1
Finnishnot grpmax-eligible	82.7%	1
European (non-Finnish)grpmax	76.4%	1
East Asian	67.2%	1
Remaining individualsnot grpmax-eligible	64.6%	2
South Asian	64%	2
Admixed American	53.6%	2
Ashkenazi Jewishnot grpmax-eligible	52.9%	2
Middle Eastern	40.4%	2
African / African-American	9.89%	10

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: FAAH2
Protein: p.Pro468=
Coding: c.1404T>C
MANE Select: NM_174912
dbSNP: rs1367830
Type: single nucleotide variant
Location: chrX:57448699 (GRCh38)
Structure: AlphaFold pLDDT 94.08

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

Similar variants

FAAH2 p.Pro468Ser Uncertain significance ★ ⚠ 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-pro468 (accessed [today's date]).

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