Is FAAH p.Thr36Pro (c.106A>C) pathogenic?

FAAH p.Thr36Pro (c.106A>C) is classified Uncertain significance in FAAH (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.0634); Very rare (popmax 0.000186%, nfe).

How common is FAAH p.Thr36Pro (c.106A>C) in the general population?

FAAH p.Thr36Pro (c.106A>C) is very rare (popmax 0.000186%, nfe) (gnomAD).

What do computational predictors say about FAAH p.Thr36Pro (c.106A>C)?

AlphaMissense predicts likely benign (score 0.0634) — an in-silico prediction, not a clinical call.

FAAH p.Thr36Pro

c.106A>C · rs1386887767 · VCV2405787

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0634 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000186%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0634	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -4.67	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 0.02	GERP -3.8
Regional constraint	o/e 0.90	unconstrained · MANE · 19 kb · p 0.0063 · regional, not allelic
Overall
CADD	5.081	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

Grpmax group 0.000186% European (non-Finnish) · 2/1,073,688 alleles

Filtering AF 3.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2e-05%

Overall 0.000145% 2/1,377,542 alleles · very rare exomes 2/1,225,394 · genomes 0/152,148 · 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.Thr36Pro
Coding: c.106A>C
MANE Select: NM_001441
dbSNP: rs1386887767
Type: single nucleotide variant
Location: chr1:46394454 (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.Thr36Met 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-thr36pro (accessed [today's date]).

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