Is C7 p.Asn202Ser (c.605A>G) pathogenic?

C7 p.Asn202Ser (c.605A>G) is classified Uncertain significance in C7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-29). AlphaMissense: likely benign (0.0914); Ultra-rare (popmax 0.0137%, nfe); Associated with complement component 7 deficiency.

What condition is associated with C7 p.Asn202Ser (c.605A>G)?

C7 p.Asn202Ser (c.605A>G) is associated with complement component 7 deficiency (ClinVar).

How common is C7 p.Asn202Ser (c.605A>G) in the general population?

C7 p.Asn202Ser (c.605A>G) is ultra-rare (popmax 0.0137%, nfe) (gnomAD).

What do computational predictors say about C7 p.Asn202Ser (c.605A>G)?

AlphaMissense predicts likely benign (score 0.0914) — an in-silico prediction, not a clinical call.

C7 p.Asn202Ser

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.605A>G · rs199587630 · VCV1013250

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0914 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0137%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

complement component 7 deficiency

Computational evidence

Protein change
AlphaMissense	0.0914	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -5.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.88	acceptor gain · deltas
Pangolin	Δ0.59	gain · loss 0.27 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Overall
CADD	29.6	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 0.0137% European (non-Finnish) · 156/1,139,176 alleles

Filtering AF 0.0119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.0124% 191/1,541,410 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0416%	2,407
European (non-Finnish)grpmax	0.0137%	7,302
Remaining individualsnot grpmax-eligible	0.0117%	8,559
East Asian	0.00229%	43,652
South Asian	0.00123%	81,044

Finnish 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.Asn202Ser
Coding: c.605A>G
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs199587630
Type: single nucleotide variant
Location: chr5:40945235 (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

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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
C7 p.Arg618Trp Uncertain significance ★★ ⚠ same condition
C7 p.Gln415Arg 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-asn202ser (accessed [today's date]).

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