Is C7 p.Asp500Ala (c.1499A>C) pathogenic?

C7 p.Asp500Ala (c.1499A>C) is classified Uncertain significance in C7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-20). AlphaMissense: ambiguous (0.409); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with C7 p.Asp500Ala (c.1499A>C)?

C7 p.Asp500Ala (c.1499A>C) is associated with Inborn genetic diseases (ClinVar).

How common is C7 p.Asp500Ala (c.1499A>C) in the general population?

C7 p.Asp500Ala (c.1499A>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about C7 p.Asp500Ala (c.1499A>C)?

AlphaMissense predicts ambiguous (score 0.409) — an in-silico prediction, not a clinical call.

C7 p.Asp500Ala

c.1499A>C · VCV3994151

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.409 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.409	ambiguous
REVEL	0.194	benign-leaning
SaProt	LLR -12.16	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP -0.14, phastCons 1
Overall
CADD	24.2	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 0.00017% European (non-Finnish) · 2/1,178,986 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,610,326 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.Asp500Ala
Coding: c.1499A>C
MANE Select: NM_001565 · reported on NM_000587
Type: single nucleotide variant
Location: chr5:40959458 (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.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
C7 p.Arg372Gln 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-asp500ala (accessed [today's date]).

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