Is C7 p.Asn197Ser (c.590A>G) pathogenic?

C7 p.Asn197Ser (c.590A>G) is classified Uncertain significance in C7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-17). AlphaMissense: likely benign (0.0815); Ultra-rare (popmax 0.0453%, afr).

How common is C7 p.Asn197Ser (c.590A>G) in the general population?

C7 p.Asn197Ser (c.590A>G) is ultra-rare (popmax 0.0453%, afr) (gnomAD).

What do computational predictors say about C7 p.Asn197Ser (c.590A>G)?

AlphaMissense predicts likely benign (score 0.0815) — an in-silico prediction, not a clinical call.

C7 p.Asn197Ser

c.590A>G · rs374503886 · VCV1498259

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0815 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0453%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0815	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -5.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.28	acceptor loss, 19 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 6.8	GERP 2.3, phastCons 1
Overall
CADD	18.27	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 0.0453% African / African-American · 32/70,618 alleles

Filtering AF 0.033% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0287%

Overall 0.00232% 35/1,507,680 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0453%	2,207
Admixed American	0.00457%	21,876
South Asian	0.00129%	77,762

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.Asn197Ser
Coding: c.590A>G
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs374503886
Type: single nucleotide variant
Location: chr5:40945220 (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 p.Asn197Lys Uncertain significance ★ ⚠ same residue
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

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-asn197ser (accessed [today's date]).

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