Is C7 p.Leu179Pro (c.536T>C) pathogenic?

C7 p.Leu179Pro (c.536T>C) is classified Uncertain significance in C7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-27). AlphaMissense: likely pathogenic (0.9425); Absent from gnomAD v4.1.

How common is C7 p.Leu179Pro (c.536T>C) in the general population?

C7 p.Leu179Pro (c.536T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C7 p.Leu179Pro (c.536T>C)?

AlphaMissense predicts likely pathogenic (score 0.9425) — an in-silico prediction, not a clinical call.

C7 p.Leu179Pro

c.536T>C · rs2111600709 · VCV1354518

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9425 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9425	likely pathogenic · top 1% in C7
REVEL	0.58	indeterminate
SaProt	LLR -10.79	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.30	donor gain, 31 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 6.1	GERP 2.5, phastCons 1
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: C7
Protein: p.Leu179Pro
Coding: c.536T>C
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs2111600709
Type: single nucleotide variant
Location: chr5:40937659 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB

Full C7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C7 p.Leu179Met Uncertain significance ★ ⚠ same residue
C7 c.281-1G>T Pathogenic/Likely pathogenic ★★ same type
C7 c.63-1G>A Pathogenic ★★ same type
C7 c.739-2A>G Likely pathogenic ★★ same type
C7 p.Arg402Ter Pathogenic/Likely pathogenic ★★ same type
C7 p.Gln271Ter Pathogenic/Likely pathogenic ★★ same type
C7 p.Gly379Arg Pathogenic/Likely pathogenic ★★ same type
C7 p.Trp205Ter Pathogenic/Likely pathogenic ★★ 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/c7-p-leu179pro (accessed [today's date]).

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