Is BNIP2 p.Asp66Val (c.197A>T) pathogenic?

BNIP2 p.Asp66Val (c.197A>T) is classified Uncertain significance in BNIP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). AlphaMissense: likely benign (0.111); Very rare (popmax 0.00492%, nfe).

How common is BNIP2 p.Asp66Val (c.197A>T) in the general population?

BNIP2 p.Asp66Val (c.197A>T) is very rare (popmax 0.00492%, nfe) (gnomAD).

What do computational predictors say about BNIP2 p.Asp66Val (c.197A>T)?

AlphaMissense predicts likely benign (score 0.111) — an in-silico prediction, not a clinical call.

BNIP2 p.Asp66Val

c.197A>T · VCV3261286

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.111 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00492%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.111	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -8.42	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 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 18 kb · p 0.027 · regional, not allelic
Overall
CADD	23.7	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 0.00492% European (non-Finnish) · 58/1,178,316 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.00405% 59/1,457,398 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00492%	20,316
Remaining individualsnot grpmax-eligible	0.00161%	62,252

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: BNIP2
Protein: p.Asp66Val
Coding: c.197A>T
MANE Select: NM_004330
Type: single nucleotide variant
Location: chr15:59679690 (GRCh38)
Gene constraint: LOEUF 1.048 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.06

Full BNIP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BNIP2 c.-101C>G Uncertain significance ★ same type
BNIP2 c.-129G>A Uncertain significance ★ same type
BNIP2 c.-150C>G Uncertain significance ★ same type
BNIP2 c.-159G>A Uncertain significance ★ same type
BNIP2 c.-159G>C Uncertain significance ★ same type
BNIP2 c.-164G>A Uncertain significance ★ same type
BNIP2 c.-173C>T Uncertain significance ★ same type
BNIP2 c.-234G>A 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/bnip2-p-asp66val (accessed [today's date]).

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