Is C7 p.Ser180Arg (c.540T>G) pathogenic?

C7 p.Ser180Arg (c.540T>G) is classified Uncertain significance in C7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-31). AlphaMissense: likely pathogenic (0.9605); Absent from gnomAD v4.1.

How common is C7 p.Ser180Arg (c.540T>G) in the general population?

C7 p.Ser180Arg (c.540T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C7 p.Ser180Arg (c.540T>G)?

AlphaMissense predicts likely pathogenic (score 0.9605) — an in-silico prediction, not a clinical call.

C7 p.Ser180Arg

c.540T>G · rs1739845529 · VCV1381927

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9605 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9605	likely pathogenic · top 1% in C7
REVEL	0.516	indeterminate
SaProt	LLR -9.62	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.27	donor loss · deltas
Constraint at this position
Conservation	phyloP -0.19	GERP -3.3, phastCons 0.68
Overall
CADD	19.06	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: C7
Protein: p.Ser180Arg
Coding: c.540T>G
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs1739845529
Type: single nucleotide variant
Location: chr5:40937663 (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 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
C7 p.Ala359Thr 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/c7-p-ser180arg (accessed [today's date]).

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