Is BCAS3 p.Pro552Ser (c.1654C>T) pathogenic?

BCAS3 p.Pro552Ser (c.1654C>T) is classified Uncertain significance in BCAS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: likely benign (0.0832); Ultra-rare (popmax 0.0179%, eas); Associated with Inborn genetic diseases.

What condition is associated with BCAS3 p.Pro552Ser (c.1654C>T)?

BCAS3 p.Pro552Ser (c.1654C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BCAS3 p.Pro552Ser (c.1654C>T) in the general population?

BCAS3 p.Pro552Ser (c.1654C>T) is ultra-rare (popmax 0.0179%, eas) (gnomAD).

What do computational predictors say about BCAS3 p.Pro552Ser (c.1654C>T)?

AlphaMissense predicts likely benign (score 0.0832) — an in-silico prediction, not a clinical call.

BCAS3 p.Pro552Ser

c.1654C>T · rs779715583 · VCV3133321

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0832 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0179%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0832	likely benign
REVEL	0.212	benign-leaning
SaProt	LLR -5.75	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 6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 689 kb · p 8.1e-12 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P567S vs ClinVar P552S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0179% East Asian · 8/44,808 alleles

Filtering AF 0.00885% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00642%

Overall 0.000684% 11/1,608,510 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0179%	5,601
South Asian	0.00222%	45,075
Remaining individualsnot grpmax-eligible	0.0016%	62,330

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: BCAS3
Protein: p.Pro552Ser
Coding: c.1654C>T
MANE Select: NM_017679
dbSNP: rs779715583
Type: single nucleotide variant
Location: chr17:61034682 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.25
Residue 552: a UniProt-annotated variant site (in hemars); the 'required for recruitment to preautophagosomal structure in response to mitophagy' region

Full BCAS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BCAS3 p.Ala349Val Uncertain significance ★★ ⚠ same condition
BCAS3 p.Arg254Cys Uncertain significance ★★ ⚠ same condition
BCAS3 p.Asp337Glu Uncertain significance ★★ ⚠ same condition
BCAS3 p.Pro755Leu Uncertain significance ★★ ⚠ same condition
BCAS3 p.Gly159= Likely benign ★★ same condition
BCAS3 c.1638-7789T>C Uncertain significance ★ ⚠ same condition
BCAS3 c.661+6T>C Uncertain significance ★ same condition
BCAS3 p.Ala125Val 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/bcas3-p-pro552ser (accessed [today's date]).

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