Is C7 p.Ile296= (c.888C>T) pathogenic?

C7 p.Ile296= (c.888C>T) is classified Likely benign in C7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-16). Very rare (popmax 0.0022%, sas).

How common is C7 p.Ile296= (c.888C>T) in the general population?

C7 p.Ile296= (c.888C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

C7 p.Ile296=

c.888C>T · rs757442071 · VCV2974667

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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 -6	GERP -4.7
Overall
CADD	2.699	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,066 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00124% 20/1,613,578 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,819
South Asiangrpmax	0.0022%	45,533
African / African-American	0.00134%	74,876
European (non-Finnish)	0.00119%	84,268

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile296=
Coding: c.888C>T
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs757442071
Type: single nucleotide variant
Location: chr5:40947751 (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-ile296 (accessed [today's date]).

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