Is BCAS4 p.Pro25= (c.75C>T) pathogenic?

BCAS4 p.Pro25= (c.75C>T) is classified Likely benign in BCAS4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-24). Ultra-rare (popmax 0.0182%, mid).

How common is BCAS4 p.Pro25= (c.75C>T) in the general population?

BCAS4 p.Pro25= (c.75C>T) is ultra-rare (popmax 0.0182%, mid) (gnomAD).

BCAS4 p.Pro25=

c.75C>T · rs777462572 · VCV748265

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0182%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.065	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6	GERP -3.1
Overall
CADD	8.877	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0182% Middle Eastern · 1/5,492 alleles

Filtering AF 0.00919% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0086%

Overall 0.00883% 129/1,461,598 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0182%	5,492
European (non-Finnish)	0.0108%	9,265
Admixed American	0.00874%	11,442
Remaining individualsnot grpmax-eligible	0.00538%	18,598
African / African-American	0.00145%	68,904
South Asian	0.00132%	75,688

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: BCAS4
Protein: p.Pro25=
Coding: c.75C>T
MANE Select: NM_198799
dbSNP: rs777462572
Type: single nucleotide variant
Location: chr20:50795158 (GRCh38)
Gene constraint: LOEUF 1.081 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.40

Full BCAS4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCAS4 p.Pro25Arg Uncertain significance ★ ⚠ same residue
BCAS4 p.Ser130Thr Benign ★★ same type
BCAS4 p.Ser130Tyr Benign/Likely benign ★★ ⚠ same type
BCAS4 p.Thr142Met Likely benign ★★ same type
BCAS4 c.-15C>T Uncertain significance ★ ⚠ same type
BCAS4 c.-6C>T Uncertain significance ★ ⚠ same type
BCAS4 p.Ala118Ser Uncertain significance ★ ⚠ same type
BCAS4 p.Ala126Thr 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/bcas4-p-pro25 (accessed [today's date]).

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