Is C7 p.Gln415Arg (c.1244A>G) pathogenic?

C7 p.Gln415Arg (c.1244A>G) is classified Uncertain significance in C7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-12). AlphaMissense: likely benign (0.1024); Very rare (popmax 0.00645%, nfe); Associated with Inborn genetic diseases.

What condition is associated with C7 p.Gln415Arg (c.1244A>G)?

C7 p.Gln415Arg (c.1244A>G) is associated with Inborn genetic diseases, complement component 7 deficiency (ClinVar).

How common is C7 p.Gln415Arg (c.1244A>G) in the general population?

C7 p.Gln415Arg (c.1244A>G) is very rare (popmax 0.00645%, nfe) (gnomAD).

What do computational predictors say about C7 p.Gln415Arg (c.1244A>G)?

AlphaMissense predicts likely benign (score 0.1024) — an in-silico prediction, not a clinical call.

C7 p.Gln415Arg

c.1244A>G · rs370190257 · VCV1493533

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1024 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00645%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1024	likely benign
REVEL	0.212	benign-leaning
SaProt	LLR -6.57	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 2.5	GERP -3.1, phastCons 0.004
Overall
CADD	9.292	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 0.00645% European (non-Finnish) · 76/1,179,194 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00502% 81/1,612,256 alleles · very rare exomes 75/1,460,060 · genomes 6/152,196 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00645%	15,516
Remaining individualsnot grpmax-eligible	0.00641%	15,601
African / African-American	0.00134%	74,878

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.Gln415Arg
Coding: c.1244A>G
MANE Select: NM_000587
dbSNP: rs370190257
Type: single nucleotide variant
Location: chr5:40955537 (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

Also linked: complement component 7 deficiency

Similar variants

C7 c.281-1G>T Pathogenic/Likely pathogenic ★★ same condition
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C7 p.Gly379Arg Pathogenic/Likely pathogenic ★★ same condition
C7 p.Trp205Ter Pathogenic/Likely pathogenic ★★ same condition
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

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-gln415arg (accessed [today's date]).

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