Is BICRA p.Ser412Pro (c.1234T>C) pathogenic?

BICRA p.Ser412Pro (c.1234T>C) is classified Uncertain significance in BICRA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). AlphaMissense: likely pathogenic (0.6022); Very rare (popmax 0.00236%, nfe).

How common is BICRA p.Ser412Pro (c.1234T>C) in the general population?

BICRA p.Ser412Pro (c.1234T>C) is very rare (popmax 0.00236%, nfe) (gnomAD).

What do computational predictors say about BICRA p.Ser412Pro (c.1234T>C)?

AlphaMissense predicts likely pathogenic (score 0.6022) — an in-silico prediction, not a clinical call.

BICRA p.Ser412Pro

c.1234T>C · VCV3824308

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6022 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00236%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6022	likely pathogenic
REVEL	0.156	moderately benign-leaning
SaProt	LLR -5.96	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 4.1, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 19 kb · p 1.1e-07 · regional, not allelic
Overall
CADD	23.1	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 0.00236% European (non-Finnish) · 27/1,145,358 alleles

Filtering AF 0.00161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00138%

Overall 0.00189% 29/1,534,254 alleles · very rare exomes 25/1,382,784 · genomes 4/151,470 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00236%	42,421
Remaining individualsnot grpmax-eligible	0.00167%	59,848
African / African-American	0.00138%	72,590

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: BICRA
Protein: p.Ser412Pro
Coding: c.1234T>C
MANE Select: NM_001394372
Type: single nucleotide variant
Location: chr19:47680404 (GRCh38)
Gene constraint: LOEUF 0.659 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 42.79

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

Similar variants

BICRA p.Gln290Ter Pathogenic/Likely pathogenic ★★ same type
BICRA p.Ala1110Thr Uncertain significance ★★ ⚠ same type
BICRA p.Ala313Pro Uncertain significance ★★ ⚠ same type
BICRA p.Ala579Thr Uncertain significance ★★ ⚠ same type
BICRA p.Arg1384Cys Uncertain significance ★★ ⚠ same type
BICRA p.Arg802Cys Uncertain significance ★★ ⚠ same type
BICRA p.Asn408Lys Uncertain significance ★★ ⚠ same type
BICRA p.Gly441Arg 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/bicra-p-ser412pro (accessed [today's date]).

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