Is FAAH p.Arg43Pro (c.128G>C) pathogenic?

FAAH p.Arg43Pro (c.128G>C) is classified Uncertain significance in FAAH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). AlphaMissense: likely benign (0.174); Very rare (popmax 0.000649%, nfe).

How common is FAAH p.Arg43Pro (c.128G>C) in the general population?

FAAH p.Arg43Pro (c.128G>C) is very rare (popmax 0.000649%, nfe) (gnomAD).

What do computational predictors say about FAAH p.Arg43Pro (c.128G>C)?

AlphaMissense predicts likely benign (score 0.174) — an in-silico prediction, not a clinical call.

FAAH p.Arg43Pro

c.128G>C · VCV3847059

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.174 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000649%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.174	likely benign
REVEL	0.243	benign-leaning
SaProt	LLR -13.20	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 19 kb · p 0.0063 · regional, not allelic
Overall
CADD	26.4	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

Grpmax group 0.000649% European (non-Finnish) · 7/1,078,674 alleles

Filtering AF 0.00027% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000174%

Overall 0.000503% 7/1,391,016 alleles · very rare exomes 7/1,238,802 · genomes 0/152,214 · joint denominator

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: FAAH
Protein: p.Arg43Pro
Coding: c.128G>C
MANE Select: NM_001441
Type: single nucleotide variant
Location: chr1:46394476 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.44

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

Similar variants

FAAH p.Arg43Gln Uncertain significance ★ ⚠ same residue
FAAH c.1316+3A>G Benign ★★ same type
FAAH p.Ala356Val Benign ★★ same type
FAAH p.Ala476Gly Benign ★★ same type
FAAH p.Arg439= Benign ★★ same type
FAAH p.Gly544= Benign ★★ same type
FAAH p.Leu426= Benign ★★ same type
FAAH p.Lys263= Benign ★★ 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/faah-p-arg43pro (accessed [today's date]).

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