Is BFSP1 p.Ala36Ser (c.106G>T) pathogenic?

BFSP1 p.Ala36Ser (c.106G>T) is classified Likely benign in BFSP1 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-11-26). AlphaMissense: likely benign (0.0852); Rare (popmax 0.425%, mid).

How common is BFSP1 p.Ala36Ser (c.106G>T) in the general population?

BFSP1 p.Ala36Ser (c.106G>T) is rare (popmax 0.425%, mid) (gnomAD).

What do computational predictors say about BFSP1 p.Ala36Ser (c.106G>T)?

AlphaMissense predicts likely benign (score 0.0852) — an in-silico prediction, not a clinical call.

BFSP1 p.Ala36Ser

c.106G>T · rs561046384 · VCV3039424

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0852 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.425%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0852	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -6.85	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 0.46	GERP -2.8
Regional constraint	o/e 0.97	unconstrained · MANE · 37 kb · p 0.4 · regional, not allelic
Overall
CADD	3.303	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 0.425% Middle Eastern · 17/3,998 alleles

Filtering AF 0.378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.374%

Overall 0.341% 4,718/1,382,782 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.488%	205
Middle Easterngrpmax	0.425%	235
European (non-Finnish)	0.388%	258
Remaining individualsnot grpmax-eligible	0.3%	334
South Asian	0.279%	359
Admixed American	0.137%	729
African / African-American	0.0724%	1,381
Finnishnot grpmax-eligible	0.052%	1,925
East Asian	0.00626%	15,984

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.Ala36Ser
Coding: c.106G>T
MANE Select: NM_001195
dbSNP: rs561046384
Type: single nucleotide variant
Location: chr20:17531224 (GRCh38)
Gene constraint: LOEUF 1.371 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.66
Residue 36: the 'head' region

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

Similar variants

BFSP1 p.Ala36Val Likely benign ★ same residue
BFSP1 p.Ala36Phe Conflicting classifications of pathogenicity ★ same residue
BFSP1 p.Ala643Thr Uncertain significance ★★ ⚠ same type
BFSP1 p.Arg560Cys Uncertain significance ★★ ⚠ same type
BFSP1 p.Arg69Trp Uncertain significance ★★ same type
BFSP1 p.Asp19Asn Uncertain significance ★★ ⚠ same type
BFSP1 p.Gln294Arg Uncertain significance ★★ ⚠ same type
BFSP1 p.Glu93Asp 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/bfsp1-p-ala36ser (accessed [today's date]).

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