Is C7 p.Ile97Val (c.289A>G) pathogenic?

C7 p.Ile97Val (c.289A>G) is classified Uncertain significance in C7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-05). AlphaMissense: likely benign (0.1096); Rare (popmax 0.127%, sas); Associated with Inborn genetic diseases.

What condition is associated with C7 p.Ile97Val (c.289A>G)?

C7 p.Ile97Val (c.289A>G) is associated with Inborn genetic diseases (ClinVar).

How common is C7 p.Ile97Val (c.289A>G) in the general population?

C7 p.Ile97Val (c.289A>G) is rare (popmax 0.127%, sas) (gnomAD).

What do computational predictors say about C7 p.Ile97Val (c.289A>G)?

AlphaMissense predicts likely benign (score 0.1096) — an in-silico prediction, not a clinical call.

C7 p.Ile97Val

c.289A>G · rs549568139 · VCV2155851

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1096 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.127%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1096	likely benign
REVEL	0.643	indeterminate
SaProt	LLR -8.16	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 2.3, phastCons 1
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 0.127% South Asian · 116/91,052 alleles

Filtering AF 0.108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.00762% 123/1,613,288 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.127%	785
Middle Eastern	0.0165%	6,058
Remaining individualsnot grpmax-eligible	0.0032%	31,231
African / African-American	0.00133%	75,004
European (non-Finnish)	0.000254%	393,137

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.Ile97Val
Coding: c.289A>G
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs549568139
Type: single nucleotide variant
Location: chr5:40936346 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

C7 p.Ile97Met Uncertain significance ★ ⚠ same residue
C7 p.Ile97= Likely benign ★ same residue
C7 p.Ala359Thr Uncertain significance ★★ ⚠ same condition
C7 p.Ala53Val Uncertain significance ★★ ⚠ same condition
C7 p.Ala611Pro Uncertain significance ★★ ⚠ same condition
C7 p.Ala839Thr Uncertain significance ★★ ⚠ same condition
C7 p.Arg220Trp Uncertain significance ★★ ⚠ same condition
C7 p.Arg226Ile Uncertain significance ★★ ⚠ same condition

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-ile97val (accessed [today's date]).

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