Is C7 p.Ser676Arg (c.2028C>G) pathogenic?

C7 p.Ser676Arg (c.2028C>G) is classified Uncertain significance in C7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-12). AlphaMissense: likely pathogenic (0.6649); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with C7 p.Ser676Arg (c.2028C>G)?

C7 p.Ser676Arg (c.2028C>G) is associated with Inborn genetic diseases (ClinVar).

How common is C7 p.Ser676Arg (c.2028C>G) in the general population?

C7 p.Ser676Arg (c.2028C>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about C7 p.Ser676Arg (c.2028C>G)?

AlphaMissense predicts likely pathogenic (score 0.6649) — an in-silico prediction, not a clinical call.

C7 p.Ser676Arg

c.2028C>G · rs1332143658 · VCV2601425

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6649 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6649	likely pathogenic · top 9% in C7
REVEL	0.468	indeterminate
SaProt	LLR -8.17	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.52	GERP 0.37, phastCons 1
Overall
CADD	22.1	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 0.00267% African / African-American · 2/74,888 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,612,646 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,444
South Asian	0.0011%	90,822

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.Ser676Arg
Coding: c.2028C>G
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs1332143658
Type: single nucleotide variant
Location: chr5:40972548 (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.Ser676Gly Uncertain significance ★ ⚠ 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
C7 p.Arg293Gln 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-ser676arg (accessed [today's date]).

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