Is FAAH2 p.Gln72Pro (c.215A>C) pathogenic?

FAAH2 p.Gln72Pro (c.215A>C) is classified Conflicting classifications of pathogenicity in FAAH2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-09-02). AlphaMissense: likely pathogenic (0.6387); Ultra-rare (popmax 0.0238%, eas).

How common is FAAH2 p.Gln72Pro (c.215A>C) in the general population?

FAAH2 p.Gln72Pro (c.215A>C) is ultra-rare (popmax 0.0238%, eas) (gnomAD).

What do computational predictors say about FAAH2 p.Gln72Pro (c.215A>C)?

AlphaMissense predicts likely pathogenic (score 0.6387) — an in-silico prediction, not a clinical call.

FAAH2 p.Gln72Pro

c.215A>C · rs769942516 · VCV2660714

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6387 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0238%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6387	likely pathogenic
REVEL	0.253	benign-leaning
SaProt	LLR -14.27	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	phastCons 0.55
Regional constraint	o/e 1.73	unconstrained · MANE · 202 kb · p 2.2e-48 · regional, not allelic
Overall
CADD	21.4	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 0.0238% East Asian · 8/33,670 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00853%

Overall 0.00108% 13/1,207,681 alleles · ultra-rare exomes 12/1,095,470 · genomes 1/112,211 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0238%	4,209
Remaining individualsnot grpmax-eligible	0.00421%	23,752
European (non-Finnish)	0.000336%	297,926

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.Gln72Pro
Coding: c.215A>C
MANE Select: NM_174912
dbSNP: rs769942516
Type: single nucleotide variant
Location: chrX:57292520 (GRCh38)
Structure: AlphaFold pLDDT 94.08

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

Similar variants

FAAH2 c.1229-14A>T Benign ★★ same type
FAAH2 p.Arg274= Benign ★★ same type
FAAH2 p.Arg42Trp Benign ★★ same type
FAAH2 p.Pro468= 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-gln72pro (accessed [today's date]).

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