Is BNC2 p.Ser984= (c.2952C>T) pathogenic?

BNC2 p.Ser984= (c.2952C>T) is classified Likely benign in BNC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). Very rare (popmax 0.00167%, amr).

How common is BNC2 p.Ser984= (c.2952C>T) in the general population?

BNC2 p.Ser984= (c.2952C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

BNC2 p.Ser984=

c.2952C>T · rs368842595 · VCV1548286

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.77	GERP -3.7
Overall
CADD	4.271	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,866 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000558% 9/1,611,804 alleles · very rare exomes 8/1,459,660 · genomes 1/152,144 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,488
Admixed Americangrpmax	0.00167%	59,866
South Asian	0.0011%	91,014
European (non-Finnish)	0.000509%	196,412

Ashkenazi Jewish 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: BNC2
Protein: p.Ser984=
Coding: c.2952C>T
MANE Select: NM_017637
dbSNP: rs368842595
Type: single nucleotide variant
Location: chr9:16419337 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.10
Residue 984: the 'disordered' region; a UniProt-annotated variant site (in luto)

Full BNC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BNC2 p.Ala386Val Uncertain significance ★★ ⚠ same type
BNC2 p.Arg536Gln Uncertain significance ★★ ⚠ same type
BNC2 p.Arg875His Uncertain significance ★★ ⚠ same type
BNC2 p.Asn1032Ser Uncertain significance ★★ ⚠ same type
BNC2 p.Asn1088Asp Uncertain significance ★★ ⚠ same type
BNC2 p.Asn668Ser Uncertain significance ★★ ⚠ same type
BNC2 p.Asn795Ser Uncertain significance ★★ ⚠ same type
BNC2 p.Asp690Glu 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/bnc2-p-ser984 (accessed [today's date]).

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