Is C7 p.Arg554Gly (c.1660A>G) pathogenic?

C7 p.Arg554Gly (c.1660A>G) is classified Uncertain significance in C7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.213); Very rare (popmax 8.59e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with C7 p.Arg554Gly (c.1660A>G)?

C7 p.Arg554Gly (c.1660A>G) is associated with Inborn genetic diseases (ClinVar).

How common is C7 p.Arg554Gly (c.1660A>G) in the general population?

C7 p.Arg554Gly (c.1660A>G) is very rare (popmax 8.59e-05%, nfe) (gnomAD).

What do computational predictors say about C7 p.Arg554Gly (c.1660A>G)?

AlphaMissense predicts likely benign (score 0.213) — an in-silico prediction, not a clinical call.

C7 p.Arg554Gly

c.1660A>G · rs2478231963 · VCV3136068

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.213 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.59e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.213	likely benign
REVEL	0.27	benign-leaning
SaProt	LLR -10.76	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.2	GERP -0.95, phastCons 0.077
Overall
CADD	23.2	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 8.59e-05% European (non-Finnish) · 1/1,164,410 alleles

Overall 6.99e-05% 1/1,430,216 alleles · very rare

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.Arg554Gly
Coding: c.1660A>G
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs2478231963
Type: single nucleotide variant
Location: chr5:40959619 (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.Arg554Ser 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-arg554gly (accessed [today's date]).

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