Is BFSP1 p.Ile271Thr (c.812T>C) pathogenic?

BFSP1 p.Ile271Thr (c.812T>C) is classified Uncertain significance in BFSP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-04). AlphaMissense: ambiguous (0.3716); Rare (popmax 0.363%, mid); Associated with cataract 33.

What condition is associated with BFSP1 p.Ile271Thr (c.812T>C)?

BFSP1 p.Ile271Thr (c.812T>C) is associated with cataract 33 (ClinVar).

How common is BFSP1 p.Ile271Thr (c.812T>C) in the general population?

BFSP1 p.Ile271Thr (c.812T>C) is rare (popmax 0.363%, mid) (gnomAD).

What do computational predictors say about BFSP1 p.Ile271Thr (c.812T>C)?

AlphaMissense predicts ambiguous (score 0.3716) — an in-silico prediction, not a clinical call.

BFSP1 p.Ile271Thr

c.812T>C · rs147718368 · VCV242475

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.3716 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.363%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

cataract 33

Computational evidence

Protein change
AlphaMissense	0.3716	ambiguous
REVEL	0.672	pathogenic-leaning
SaProt	LLR -8.39	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 37 kb · p 0.4 · regional, not allelic
Overall
CADD	26.1	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 0.363% Middle Eastern · 22/6,062 alleles

Filtering AF 0.246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.207%

Overall 0.0296% 478/1,614,132 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.443%	226
Middle Easterngrpmax	0.363%	276
Remaining individualsnot grpmax-eligible	0.0448%	2,233
Admixed American	0.0233%	4,287
European (non-Finnish)	0.0217%	4,609
South Asian	0.0209%	4,794
African / African-American	0.0107%	9,378

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: BFSP1
Protein: p.Ile271Thr
Coding: c.812T>C
MANE Select: NM_001195
dbSNP: rs147718368
Type: single nucleotide variant
Location: chr20:17498964 (GRCh38)
Gene constraint: LOEUF 1.371 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.66
Residue 271: the if rod domain; the 'coil 2' region

Full BFSP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cataract 33 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BFSP1 p.Ala643Thr Uncertain significance ★★ ⚠ same condition
BFSP1 p.Arg560Cys Uncertain significance ★★ ⚠ same condition
BFSP1 p.Arg69Trp Uncertain significance ★★ ⚠ same condition
BFSP1 p.Asp19Asn Uncertain significance ★★ ⚠ same condition
BFSP1 p.Gln294Arg Uncertain significance ★★ ⚠ same condition
BFSP1 p.Gly46Trp Uncertain significance ★★ ⚠ same condition
BFSP1 p.Leu68Phe Uncertain significance ★★ ⚠ same condition
BFSP1 p.Ser125Asn Uncertain significance ★★ ⚠ same condition

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/bfsp1-p-ile271thr (accessed [today's date]).

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