Is BICC1 p.Ser712= (c.2136C>T) pathogenic?

BICC1 p.Ser712= (c.2136C>T) is classified Likely benign in BICC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-07). Ultra-rare (popmax 0.0165%, mid).

How common is BICC1 p.Ser712= (c.2136C>T) in the general population?

BICC1 p.Ser712= (c.2136C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

BICC1 p.Ser712=

c.2136C>T · rs267602532 · VCV3613817

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 -12	GERP -5.4
Overall
CADD	0.717	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,070 alleles

Filtering AF 0.00197% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00236% 38/1,608,900 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,070
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,546
European (non-Finnish)	0.00272%	36,799
East Asian	0.00224%	44,712
Admixed American	0.00168%	59,360
Remaining individualsnot grpmax-eligible	0.0016%	62,314
South Asian	0.00112%	89,602

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: BICC1
Protein: p.Ser712=
Coding: c.2136C>T
MANE Select: NM_001080512
dbSNP: rs267602532
Type: single nucleotide variant
Location: chr10:58803197 (GRCh38)
Gene constraint: LOEUF 0.541 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 61.02 · 3 PDB
Residue 712: the 'disordered' region

Full BICC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BICC1 p.Ala190Thr Uncertain significance ★★ ⚠ same type
BICC1 p.Ala276Ser Uncertain significance ★★ ⚠ same type
BICC1 p.Ala523Val Uncertain significance ★★ ⚠ same type
BICC1 p.Arg302Gln Uncertain significance ★★ ⚠ same type
BICC1 p.Arg657Lys Uncertain significance ★★ ⚠ same type
BICC1 p.Arg804His Uncertain significance ★★ ⚠ same type
BICC1 p.Arg839His Uncertain significance ★★ ⚠ same type
BICC1 p.Arg961Cys 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/bicc1-p-ser712 (accessed [today's date]).

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