Is FAAH p.Ser157Arg (c.469A>C) pathogenic?

FAAH p.Ser157Arg (c.469A>C) is classified Uncertain significance in FAAH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-07). AlphaMissense: likely pathogenic (0.5997); Very rare (popmax 0.00223%, eas).

How common is FAAH p.Ser157Arg (c.469A>C) in the general population?

FAAH p.Ser157Arg (c.469A>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about FAAH p.Ser157Arg (c.469A>C)?

AlphaMissense predicts likely pathogenic (score 0.5997) — an in-silico prediction, not a clinical call.

FAAH p.Ser157Arg

c.469A>C · rs746348249 · VCV2558442

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5997 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5997	likely pathogenic
REVEL	0.055	moderately benign-leaning
SaProt	LLR -8.18	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.94, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 19 kb · p 0.0063 · regional, not allelic
Overall
CADD	18.28	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 0.00223% East Asian · 1/44,898 alleles

Overall 6.2e-05% 1/1,612,124 alleles · very rare exomes 0/1,460,002 · genomes 1/152,122 · 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.Ser157Arg
Coding: c.469A>C
MANE Select: NM_001441
dbSNP: rs746348249
Type: single nucleotide variant
Location: chr1:46405396 (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 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
FAAH p.Pro129Thr Benign/Likely 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-ser157arg (accessed [today's date]).

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