Is FAAH2 p.Ile85Val (c.253A>G) pathogenic?

FAAH2 p.Ile85Val (c.253A>G) is classified Uncertain significance in FAAH2 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-10-03). AlphaMissense: likely benign (0.1041); Ultra-rare (popmax 0.0461%, sas).

How common is FAAH2 p.Ile85Val (c.253A>G) in the general population?

FAAH2 p.Ile85Val (c.253A>G) is ultra-rare (popmax 0.0461%, sas) (gnomAD).

What do computational predictors say about FAAH2 p.Ile85Val (c.253A>G)?

AlphaMissense predicts likely benign (score 0.1041) — an in-silico prediction, not a clinical call.

FAAH2 p.Ile85Val

c.253A>G · rs762458246 · VCV2315055

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1041 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0461%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1041	likely benign
REVEL	0.191	benign-leaning
SaProt	LLR -6.26	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 0.12
Regional constraint	o/e 1.73	unconstrained · MANE · 202 kb · p 2.2e-48 · regional, not allelic
Overall
CADD	14.41	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 0.0461% South Asian · 26/56,403 alleles

Filtering AF 0.0322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0277%

Overall 0.0029% 35/1,207,785 alleles · ultra-rare exomes 34/1,095,655 · genomes 1/112,130 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0461%	2,169
Middle Eastern	0.0229%	4,371
Remaining individualsnot grpmax-eligible	0.00631%	15,837
European (non-Finnish)	0.000559%	178,754

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.Ile85Val
Coding: c.253A>G
MANE Select: NM_174912
dbSNP: rs762458246
Type: single nucleotide variant
Location: chrX:57292558 (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-ile85val (accessed [today's date]).

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