Is BCDIN3D p.Pro272Ser (c.814C>T) pathogenic?

BCDIN3D p.Pro272Ser (c.814C>T) is classified Uncertain significance in BCDIN3D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.0743); Very rare (popmax 0.000254%, nfe).

How common is BCDIN3D p.Pro272Ser (c.814C>T) in the general population?

BCDIN3D p.Pro272Ser (c.814C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about BCDIN3D p.Pro272Ser (c.814C>T)?

AlphaMissense predicts likely benign (score 0.0743) — an in-silico prediction, not a clinical call.

BCDIN3D p.Pro272Ser

c.814C>T · VCV4200725

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0743 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0743	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -6.34	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 0.94	GERP 1.9, phastCons 0.003
Regional constraint	o/e 0.90	unconstrained · MANE · 4,713 bp · p 0.065 · regional, not allelic
Overall
CADD	15.7	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,006 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,612,996 alleles · very rare exomes 2/1,460,858 · genomes 1/152,138 · joint denominator

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: BCDIN3D
Protein: p.Pro272Ser
Coding: c.814C>T
MANE Select: NM_181708
Type: single nucleotide variant
Location: chr12:49838436 (GRCh38)
Gene constraint: LOEUF 1.069 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.99 · 1 PDB
Residue 272: the bin3-type sam domain

Full BCDIN3D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCDIN3D p.Asp8Gly Benign ★★ same type
BCDIN3D p.Ala205Thr Uncertain significance ★ ⚠ same type
BCDIN3D p.Ala206Thr Uncertain significance ★ same type
BCDIN3D p.Ala225Val Uncertain significance ★ ⚠ same type
BCDIN3D p.Ala2Ser Uncertain significance ★ ⚠ same type
BCDIN3D p.Arg142Trp Uncertain significance ★ ⚠ same type
BCDIN3D p.Arg209His Uncertain significance ★ same type
BCDIN3D p.Asp79Gly 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/bcdin3d-p-pro272ser (accessed [today's date]).

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