Is FAR1 p.Arg296Ser (c.888A>C) pathogenic?

FAR1 p.Arg296Ser (c.888A>C) is classified Uncertain significance in FAR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-02). AlphaMissense: likely pathogenic (0.6596); Absent from gnomAD v4.1.

How common is FAR1 p.Arg296Ser (c.888A>C) in the general population?

FAR1 p.Arg296Ser (c.888A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FAR1 p.Arg296Ser (c.888A>C)?

AlphaMissense predicts likely pathogenic (score 0.6596) — an in-silico prediction, not a clinical call.

FAR1 p.Arg296Ser

c.888A>C · rs2500136496 · VCV1720765

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6596 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6596	likely pathogenic
REVEL	0.101	moderately benign-leaning
SaProt	LLR -9.37	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 7.1	GERP 0.56, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 34 kb · p 2.6e-21 · regional, not allelic
Overall
CADD	24.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FAR1
Protein: p.Arg296Ser
Coding: c.888A>C
MANE Select: NM_032228
dbSNP: rs2500136496
Type: single nucleotide variant
Location: chr11:13712966 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI 0.57 (gnomAD)
Structure: AlphaFold pLDDT 94.13
Residue 296: a UniProt-annotated variant site (in pfcrd; results in a complete loss of enzyme activity)

Full FAR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FAR1 c.-7-2A>G Likely pathogenic ★★ same type
FAR1 p.Arg480Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
FAR1 p.Arg480His Pathogenic/Likely pathogenic ★★ same type
FAR1 p.Arg480Leu Pathogenic ★★ same type
FAR1 c.546-13A>G Uncertain significance ★★ same type
FAR1 p.Ala361Val Uncertain significance ★★ ⚠ same type
FAR1 p.Arg133Gln Uncertain significance ★★ ⚠ same type
FAR1 p.Arg160Cys 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/far1-p-arg296ser (accessed [today's date]).

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