Is C7 p.Ala485Val (c.1454C>T) pathogenic?

C7 p.Ala485Val (c.1454C>T) is classified Uncertain significance in C7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-07). AlphaMissense: ambiguous (0.4768); Ultra-rare (popmax 0.0958%, eas).

How common is C7 p.Ala485Val (c.1454C>T) in the general population?

C7 p.Ala485Val (c.1454C>T) is ultra-rare (popmax 0.0958%, eas) (gnomAD).

What do computational predictors say about C7 p.Ala485Val (c.1454C>T)?

AlphaMissense predicts ambiguous (score 0.4768) — an in-silico prediction, not a clinical call.

C7 p.Ala485Val

c.1454C>T · rs200622924 · VCV1359426

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4768 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0958%, eas)

Computational evidence

Protein change
AlphaMissense	0.4768	ambiguous
REVEL	0.449	indeterminate
SaProt	LLR -8.39	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.5, phastCons 1
Overall
CADD	22.2	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 0.0958% East Asian · 43/44,870 alleles

Filtering AF 0.0731% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.065%

Overall 0.0118% 190/1,611,062 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0958%	1,043
Ashkenazi Jewishnot grpmax-eligible	0.0306%	3,267
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0144%	6,928
Admixed American	0.0117%	8,553
South Asian	0.00994%	10,061
African / African-American	0.00935%	10,695
European (non-Finnish)	0.00866%	11,552
Finnishnot grpmax-eligible	0.0047%	21,297

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.Ala485Val
Coding: c.1454C>T
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs200622924
Type: single nucleotide variant
Location: chr5:40958226 (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.Ala485= Likely benign ★★ same residue
C7 p.Ala485Thr 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

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-ala485val (accessed [today's date]).

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