Is BICRA p.Pro1105Ser (c.3313C>T) pathogenic?

BICRA p.Pro1105Ser (c.3313C>T) is classified Uncertain significance in BICRA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-22). AlphaMissense: likely benign (0.1901); Very rare (popmax 0.00167%, amr); Associated with Coffin-Siris syndrome 1.

What condition is associated with BICRA p.Pro1105Ser (c.3313C>T)?

BICRA p.Pro1105Ser (c.3313C>T) is associated with Coffin-Siris syndrome 1 (ClinVar).

How common is BICRA p.Pro1105Ser (c.3313C>T) in the general population?

BICRA p.Pro1105Ser (c.3313C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about BICRA p.Pro1105Ser (c.3313C>T)?

AlphaMissense predicts likely benign (score 0.1901) — an in-silico prediction, not a clinical call.

BICRA p.Pro1105Ser

c.3313C>T · VCV3377646

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1901 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Coffin-Siris syndrome 1

Computational evidence

Protein change
AlphaMissense	0.1901	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -4.70	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 5.8	GERP 5, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 19 kb · p 1.1e-07 · regional, not allelic
Overall
CADD	22.8	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 0.00167% Admixed American · 1/60,008 alleles

Overall 0.000125% 2/1,599,192 alleles · very rare exomes 2/1,446,968 · genomes 0/152,224 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,008
South Asian	0.0011%	90,818

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.Pro1105Ser
Coding: c.3313C>T
MANE Select: NM_001394372
Type: single nucleotide variant
Location: chr19:47698698 (GRCh38)
Gene constraint: LOEUF 0.659 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 42.79
Residue 1105: a UniProt-annotated variant site (in css12)

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

Disease context

Coffin-Siris syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-pro1105ser (accessed [today's date]).

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