Is C7 p.Ala484Val (c.1451C>T) pathogenic?

C7 p.Ala484Val (c.1451C>T) is classified Conflicting classifications of pathogenicity in C7 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-09-20). AlphaMissense: likely benign (0.0686); Ultra-rare (popmax 0.024%, afr); Associated with complement component 7 deficiency.

What condition is associated with C7 p.Ala484Val (c.1451C>T)?

C7 p.Ala484Val (c.1451C>T) is associated with complement component 7 deficiency (ClinVar).

How common is C7 p.Ala484Val (c.1451C>T) in the general population?

C7 p.Ala484Val (c.1451C>T) is ultra-rare (popmax 0.024%, afr) (gnomAD).

What do computational predictors say about C7 p.Ala484Val (c.1451C>T)?

AlphaMissense predicts likely benign (score 0.0686) — an in-silico prediction, not a clinical call.

C7 p.Ala484Val

Q: How is Immunodeficiency due to a late component of complement deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1451C>T · rs369097905 · VCV1014362

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0686 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

complement component 7 deficiency

Computational evidence

Protein change
AlphaMissense	0.0686	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -7.79	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 -2.3	GERP -2.7
Overall
CADD	1.573	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 0.024% African / African-American · 18/74,968 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.009% 145/1,611,244 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,165
Admixed American	0.0234%	4,275
South Asian	0.0155%	6,471
Remaining individualsnot grpmax-eligible	0.0144%	6,930
East Asian	0.0111%	8,969
European (non-Finnish)	0.00696%	14,370
Finnishnot grpmax-eligible	0.00469%	21,303

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.Ala484Val
Coding: c.1451C>T
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs369097905
Type: single nucleotide variant
Location: chr5:40958223 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB

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

Disease context

complement component 7 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Immunodeficiency due to a late component of complement deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

C7 p.Ala484= Benign/Likely benign ★★ same residue
C7 p.Ala484Thr Uncertain significance ★ ⚠ same residue
C7 c.281-1G>T Pathogenic/Likely pathogenic ★★ same condition
C7 c.63-1G>A Pathogenic ★★ same condition
C7 p.Gly379Arg Pathogenic/Likely pathogenic ★★ same condition
C7 p.Trp205Ter Pathogenic/Likely pathogenic ★★ same condition
C7 p.Arg220Gln Uncertain significance ★★ ⚠ same condition
C7 p.Arg402Gln 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-ala484val (accessed [today's date]).

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