Is C7 p.Arg554Ser (c.1662G>C) pathogenic?

C7 p.Arg554Ser (c.1662G>C) is classified Uncertain significance in C7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-29). AlphaMissense: ambiguous (0.3496); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with C7 p.Arg554Ser (c.1662G>C)?

C7 p.Arg554Ser (c.1662G>C) is associated with Inborn genetic diseases (ClinVar).

How common is C7 p.Arg554Ser (c.1662G>C) in the general population?

C7 p.Arg554Ser (c.1662G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C7 p.Arg554Ser (c.1662G>C)?

AlphaMissense predicts ambiguous (score 0.3496) — an in-silico prediction, not a clinical call.

C7 p.Arg554Ser

c.1662G>C · rs754794455 · VCV2314653

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3496 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3496	ambiguous
REVEL	0.256	benign-leaning
SaProt	LLR -8.88	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.47	acceptor loss at this position · masked 0 · deltas
Pangolin	Δ0.45	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.23	GERP -5.7, phastCons 0.34
Overall
CADD	14.33	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: C7
Protein: p.Arg554Ser
Coding: c.1662G>C
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs754794455
Type: single nucleotide variant
Location: chr5:40962085 (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.Arg554Gly 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-arg554ser (accessed [today's date]).

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