Is BNIP3L p.Pro40Ser (c.118C>T) pathogenic?

BNIP3L p.Pro40Ser (c.118C>T) is classified Uncertain significance in BNIP3L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-01). AlphaMissense: likely benign (0.1605); Absent from gnomAD v4.1.

How common is BNIP3L p.Pro40Ser (c.118C>T) in the general population?

BNIP3L p.Pro40Ser (c.118C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BNIP3L p.Pro40Ser (c.118C>T)?

AlphaMissense predicts likely benign (score 0.1605) — an in-silico prediction, not a clinical call.

BNIP3L p.Pro40Ser

c.118C>T · VCV3825016

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1605 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,118)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1605	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -7.67	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 6	GERP 7, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 8,137 bp · p 0.036 · regional, not allelic
Overall
CADD	22.2	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

No allele count reported in gnomAD v4.1 (AN 1,608,118). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BNIP3L
Protein: p.Pro40Ser
Coding: c.118C>T
MANE Select: NM_004331
Type: single nucleotide variant
Location: chr8:26391260 (GRCh38)
Gene constraint: LOEUF 0.659 · pLI 0.47 (gnomAD)
Structure: AlphaFold pLDDT 60.73
Residue 40: the 'disordered' region

Full BNIP3L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BNIP3L p.Ala183Ser Uncertain significance ★ ⚠ same type
BNIP3L p.Arg163Cys Uncertain significance ★ ⚠ same type
BNIP3L p.Asn14Ser Uncertain significance ★ ⚠ same type
BNIP3L p.Glu123Val Uncertain significance ★ ⚠ same type
BNIP3L p.Glu58Ala Uncertain significance ★ ⚠ same type
BNIP3L p.Gly178Ala Uncertain significance ★ ⚠ same type
BNIP3L p.Ile180Phe Uncertain significance ★ ⚠ same type
BNIP3L p.Ile205Val 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/bnip3l-p-pro40ser (accessed [today's date]).

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