Is C7 p.Cys545= (c.1635C>T) pathogenic?

C7 p.Cys545= (c.1635C>T) is classified Benign/Likely benign in C7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-12). Rare (popmax 0.372%, amr).

How common is C7 p.Cys545= (c.1635C>T) in the general population?

C7 p.Cys545= (c.1635C>T) is rare (popmax 0.372%, amr) (gnomAD).

C7 p.Cys545=

c.1635C>T · rs201282493 · VCV1599146

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.372%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.2	GERP -5.5
Overall
CADD	0.146	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.372% Admixed American · 219/58,928 alleles

Filtering AF 0.331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.316%

Overall 0.0159% 255/1,603,374 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.372%	269
East Asian	0.00894%	11,185
Remaining individualsnot grpmax-eligible	0.00646%	15,471
South Asian	0.00223%	44,763
European (non-Finnish)	0.00213%	47,008
Finnishnot grpmax-eligible	0.00157%	63,742

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: C7
Protein: p.Cys545=
Coding: c.1635C>T
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs201282493
Type: single nucleotide variant
Location: chr5:40959594 (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.Cys545Arg Uncertain significance ★★ ⚠ same residue
C7 p.Cys545Ter Pathogenic ★ same residue
C7 p.Cys545Trp Uncertain significance ★ ⚠ same residue
C7 p.Cys545Tyr 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

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-cys545 (accessed [today's date]).

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