Is BCL2A1 p.Pro110Ser (c.328C>T) pathogenic?

BCL2A1 p.Pro110Ser (c.328C>T) is classified Uncertain significance in BCL2A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely benign (0.0967); Very rare (popmax 0.00267%, afr).

How common is BCL2A1 p.Pro110Ser (c.328C>T) in the general population?

BCL2A1 p.Pro110Ser (c.328C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about BCL2A1 p.Pro110Ser (c.328C>T)?

AlphaMissense predicts likely benign (score 0.0967) — an in-silico prediction, not a clinical call.

BCL2A1 p.Pro110Ser

c.328C>T · rs372157153 · VCV2510958

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0967 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0967	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -6.08	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 1	GERP 1.6, phastCons 0.048
Regional constraint	o/e 0.77	unconstrained · MANE · 10 kb · p 0.001 · regional, not allelic
Overall
CADD	8.684	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 0.00267% African / African-American · 2/74,908 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00198% 32/1,613,990 alleles · very rare exomes 28/1,461,866 · genomes 4/152,124 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,454
European (non-Finnish)	0.00254%	39,334

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: BCL2A1
Protein: p.Pro110Ser
Coding: c.328C>T
MANE Select: NM_004049
dbSNP: rs372157153
Type: single nucleotide variant
Location: chr15:79970792 (GRCh38)
Gene constraint: LOEUF 1.094 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.63 · 26 PDB

Full BCL2A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCL2A1 p.Pro110Leu Uncertain significance ★ ⚠ same residue
BCL2A1 p.Thr33= Benign ★★ same type
BCL2A1 p.Asn58Ser Uncertain significance ★ ⚠ same type
BCL2A1 p.Asn72Asp Uncertain significance ★ ⚠ same type
BCL2A1 p.Cys165Arg Uncertain significance ★ ⚠ same type
BCL2A1 p.Gly97Ala Uncertain significance ★ ⚠ same type
BCL2A1 p.Leu170Pro Uncertain significance ★ ⚠ same type
BCL2A1 p.Leu99Val 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/bcl2a1-p-pro110ser (accessed [today's date]).

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