Is C7 p.Ala840Val (c.2519C>T) pathogenic?

C7 p.Ala840Val (c.2519C>T) is classified Uncertain significance in C7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-17). AlphaMissense: likely benign (0.0773); Very rare (popmax 0.00332%, sas).

How common is C7 p.Ala840Val (c.2519C>T) in the general population?

C7 p.Ala840Val (c.2519C>T) is very rare (popmax 0.00332%, sas) (gnomAD).

What do computational predictors say about C7 p.Ala840Val (c.2519C>T)?

AlphaMissense predicts likely benign (score 0.0773) — an in-silico prediction, not a clinical call.

C7 p.Ala840Val

c.2519C>T · rs761687811 · VCV2149934

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0773 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00332%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0773	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -6.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.6	GERP -5
Overall
CADD	0.247	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00332% South Asian · 3/90,476 alleles

Filtering AF 0.000881% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000444%

Overall 0.000996% 16/1,606,838 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00332%	30,159
Admixed American	0.00167%	59,728
European (non-Finnish)	0.00102%	97,895

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.Ala840Val
Coding: c.2519C>T
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs761687811
Type: single nucleotide variant
Location: chr5:40981560 (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.Ala840= Likely benign ★ 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
C7 p.Trp205Ter 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-ala840val (accessed [today's date]).

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