Is C7 p.Thr45Ile (c.134C>T) pathogenic?

C7 p.Thr45Ile (c.134C>T) is classified Likely benign in C7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.1346); Rare (popmax 0.617%, amr).

How common is C7 p.Thr45Ile (c.134C>T) in the general population?

C7 p.Thr45Ile (c.134C>T) is rare (popmax 0.617%, amr) (gnomAD).

What do computational predictors say about C7 p.Thr45Ile (c.134C>T)?

AlphaMissense predicts likely benign (score 0.1346) — an in-silico prediction, not a clinical call.

C7 p.Thr45Ile

c.134C>T · rs78327832 · VCV1084122

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1346 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.617%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1346	likely benign
REVEL	0.192	benign-leaning
SaProt	LLR -9.72	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 3.9	GERP 2.1, phastCons 1
Overall
CADD	23.1	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

Grpmax group 0.617% Admixed American · 370/60,002 alleles

Filtering AF 0.565% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.545%

Overall 0.0518% 834/1,611,540 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.617%	162
East Asian	0.234%	427
Remaining individualsnot grpmax-eligible	0.0577%	1,733
South Asian	0.0484%	2,068
European (non-Finnish)	0.0223%	4,478
African / African-American	0.02%	4,997
Middle Eastern	0.0165%	6,056

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.Thr45Ile
Coding: c.134C>T
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs78327832
Type: single nucleotide variant
Location: chr5:40931135 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB
Residue 45: a disulfide bond; a β-strand

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-thr45ile (accessed [today's date]).

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