Is BCAS3 p.Thr472= (c.1416G>A) pathogenic?

BCAS3 p.Thr472= (c.1416G>A) is classified Benign in BCAS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-01). Low-frequency (popmax 1.38%, nfe).

How common is BCAS3 p.Thr472= (c.1416G>A) in the general population?

BCAS3 p.Thr472= (c.1416G>A) is low-frequency (popmax 1.38%, nfe) (gnomAD).

BCAS3 p.Thr472=

c.1416G>A · rs36055285 · VCV2647995

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.38%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.9	GERP -5.4
Overall
CADD	2.664	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.38% European (non-Finnish) · 16,341/1,180,028 alleles

Filtering AF 1.37% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.36%

Overall 1.2% 19,427/1,614,172 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	3.07%	33
European (non-Finnish)grpmax	1.38%	72
Remaining individualsnot grpmax-eligible	1.02%	98
Ashkenazi Jewishnot grpmax-eligible	0.355%	282
Admixed American	0.34%	294
African / African-American	0.189%	529
Amishnot grpmax-eligible	0.11%	912
Middle Eastern	0.0661%	1,514
South Asian	0.0318%	3,141
East Asian	0.00223%	44,872

Finnish 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: BCAS3
Protein: p.Thr472=
Coding: c.1416G>A
MANE Select: NM_017679
dbSNP: rs36055285
Type: single nucleotide variant
Location: chr17:60990165 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.25
Residue 472: a UniProt-annotated variant site (in hemars); the 'required for recruitment to preautophagosomal structure in response to mitophagy' region; the 'disordered' region

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

Similar variants

BCAS3 p.Ala349Val Uncertain significance ★★ ⚠ same type
BCAS3 p.Arg254Cys Uncertain significance ★★ ⚠ same type
BCAS3 p.Asp337Glu Uncertain significance ★★ ⚠ same type
BCAS3 p.Pro755Leu Uncertain significance ★★ ⚠ same type
BCAS3 c.1638-10A>G Likely benign ★★ same type
BCAS3 p.Gly159= Likely benign ★★ same type
BCAS3 c.1762+1G>A Likely pathogenic ★ same type
BCAS3 p.Arg544Ter Likely pathogenic ★ 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/bcas3-p-thr472 (accessed [today's date]).

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