Is BPIFA2 p.Val60Ile (c.178G>A) pathogenic?

BPIFA2 p.Val60Ile (c.178G>A) is classified Uncertain significance in BPIFA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: likely benign (0.1094); Very rare (popmax 0.00153%, nfe).

How common is BPIFA2 p.Val60Ile (c.178G>A) in the general population?

BPIFA2 p.Val60Ile (c.178G>A) is very rare (popmax 0.00153%, nfe) (gnomAD).

What do computational predictors say about BPIFA2 p.Val60Ile (c.178G>A)?

AlphaMissense predicts likely benign (score 0.1094) — an in-silico prediction, not a clinical call.

BPIFA2 p.Val60Ile

c.178G>A · VCV3825148

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1094 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1094	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -5.18	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 -20	GERP -3.2
Regional constraint	o/e 1.01	unconstrained · MANE · 11 kb · p 0.91 · regional, not allelic
Overall
CADD	0.012	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 0.00153% European (non-Finnish) · 18/1,179,534 alleles

Filtering AF 0.000954% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.0013% 19/1,460,448 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00153%	65,530
South Asian	0.0011%	90,704

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: BPIFA2
Protein: p.Val60Ile
Coding: c.178G>A
MANE Select: NM_080574
Type: single nucleotide variant
Location: chr20:33172952 (GRCh38)
Gene constraint: LOEUF 1.122 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.37

Full BPIFA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BPIFA2 p.Gly101= Benign ★★ same type
BPIFA2 p.Ala131Val Uncertain significance ★ ⚠ same type
BPIFA2 p.Ala155Pro Uncertain significance ★ ⚠ same type
BPIFA2 p.Ala155Thr Uncertain significance ★ ⚠ same type
BPIFA2 p.Asp118Asn Uncertain significance ★ ⚠ same type
BPIFA2 p.Asp187Glu Uncertain significance ★ ⚠ same type
BPIFA2 p.Asp28Glu Uncertain significance ★ ⚠ same type
BPIFA2 p.Gln3Pro 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/bpifa2-p-val60ile (accessed [today's date]).

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