Is BFAR p.Pro304Leu (c.911C>T) pathogenic?

BFAR p.Pro304Leu (c.911C>T) is classified Uncertain significance in BFAR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). AlphaMissense: likely benign (0.1796); Absent from gnomAD v4.1.

How common is BFAR p.Pro304Leu (c.911C>T) in the general population?

BFAR p.Pro304Leu (c.911C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BFAR p.Pro304Leu (c.911C>T)?

AlphaMissense predicts likely benign (score 0.1796) — an in-silico prediction, not a clinical call.

BFAR p.Pro304Leu

c.911C>T · VCV3824218

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1796 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1796	likely benign
REVEL	0.522	indeterminate
SaProt	LLR -12.42	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 23 kb · p 0.11 · regional, not allelic
Overall
CADD	25.3	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: BFAR
Protein: p.Pro304Leu
Coding: c.911C>T
MANE Select: NM_016561
Type: single nucleotide variant
Location: chr16:14662019 (GRCh38)
Gene constraint: LOEUF 1.159 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.40

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

Similar variants

BFAR p.Arg245His Benign ★★ ⚠ same type
BFAR p.Ala156Val Uncertain significance ★ ⚠ same type
BFAR p.Ala238Thr Uncertain significance ★ ⚠ same type
BFAR p.Ala238Val Uncertain significance ★ ⚠ same type
BFAR p.Ala59Val Uncertain significance ★ ⚠ same type
BFAR p.Ala90Val Uncertain significance ★ ⚠ same type
BFAR p.Ala98Thr Uncertain significance ★ ⚠ same type
BFAR p.Arg135Pro 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/bfar-p-pro304leu (accessed [today's date]).

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