Is BPIFC p.Ser136Cys (c.407C>G) pathogenic?

BPIFC p.Ser136Cys (c.407C>G) is classified Uncertain significance in BPIFC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-19). AlphaMissense: likely benign (0.2878); Absent from gnomAD v4.1.

How common is BPIFC p.Ser136Cys (c.407C>G) in the general population?

BPIFC p.Ser136Cys (c.407C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BPIFC p.Ser136Cys (c.407C>G)?

AlphaMissense predicts likely benign (score 0.2878) — an in-silico prediction, not a clinical call.

BPIFC p.Ser136Cys

c.407C>G · VCV3992509

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2878 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2878	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -13.05	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 43 kb · p 0.43 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BPIFC
Protein: p.Ser136Cys
Coding: c.407C>G
MANE Select: NM_174932
Type: single nucleotide variant
Location: chr22:32445964 (GRCh38)
Gene constraint: LOEUF 1.253 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.60

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

Similar variants

BPIFC p.Ala184Val Uncertain significance ★ ⚠ same type
BPIFC p.Ala204Ser Uncertain significance ★ ⚠ same type
BPIFC p.Ala209Val Uncertain significance ★ ⚠ same type
BPIFC p.Ala96Ser Uncertain significance ★ ⚠ same type
BPIFC p.Ala96Val Uncertain significance ★ ⚠ same type
BPIFC p.Arg273Cys Uncertain significance ★ ⚠ same type
BPIFC p.Arg326Gln Uncertain significance ★ ⚠ same type
BPIFC p.Arg326Trp 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/bpifc-p-ser136cys (accessed [today's date]).

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