Is C7 p.Arg50Trp (c.148C>T) pathogenic?

C7 p.Arg50Trp (c.148C>T) is classified Uncertain significance in C7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). AlphaMissense: ambiguous (0.4705); Very rare (popmax 0.00608%, nfe); Associated with Inborn genetic diseases.

What condition is associated with C7 p.Arg50Trp (c.148C>T)?

C7 p.Arg50Trp (c.148C>T) is associated with Inborn genetic diseases (ClinVar).

How common is C7 p.Arg50Trp (c.148C>T) in the general population?

C7 p.Arg50Trp (c.148C>T) is very rare (popmax 0.00608%, nfe) (gnomAD).

What do computational predictors say about C7 p.Arg50Trp (c.148C>T)?

AlphaMissense predicts ambiguous (score 0.4705) — an in-silico prediction, not a clinical call.

C7 p.Arg50Trp

c.148C>T · rs376674018 · VCV3136067

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4705 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00608%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4705	ambiguous
REVEL	0.746	pathogenic-leaning
SaProt	LLR -13.79	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP -1.2, phastCons 0.99
Overall
CADD	24.3	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 0.00608% European (non-Finnish) · 71/1,168,404 alleles

Filtering AF 0.00491% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00451%

Overall 0.00483% 77/1,592,564 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00608%	16,456
East Asian	0.00451%	22,169
South Asian	0.00231%	43,202
Remaining individualsnot grpmax-eligible	0.00162%	61,604
African / African-American	0.00134%	74,490

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.Arg50Trp
Coding: c.148C>T
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs376674018
Type: single nucleotide variant
Location: chr5:40934334 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB
Residue 50: a disulfide bond; a β-strand

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.Arg50Gln 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-arg50trp (accessed [today's date]).

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