Is C5 p.Val802Ile (c.2404G>A) pathogenic?

C5 p.Val802Ile (c.2404G>A) is classified Benign/Likely benign in C5 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0676); Common (popmax 63.3%, sas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about C5 p.Val802Ile (c.2404G>A)?

AlphaMissense predicts likely benign (score 0.0676) — an in-silico prediction, not a clinical call.

C5 p.Val802Ile

Q: How common is C5 p.Val802Ile (c.2404G>A) in the general population?

C5 p.Val802Ile (c.2404G>A) is common (popmax 63.3%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2404G>A · rs17611 · VCV402454

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0676 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 63.3%, sas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0676	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -6.47	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 0.53	GERP -1.5, phastCons 0.95
Regional constraint	o/e 0.86	unconstrained · MANE · 98 kb · p 1.2e-09 · regional, not allelic
Overall
CADD	15.72	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 63.3% South Asian · 57,475/90,822 alleles

Filtering AF 62.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 62.7%

Overall 44.3% 711,244/1,604,840 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	64.4%	2
South Asiangrpmax	63.3%	2
East Asian	53.7%	2
Admixed American	52.8%	2
Ashkenazi Jewishnot grpmax-eligible	51.3%	2
Middle Eastern	50.5%	2
Finnishnot grpmax-eligible	49.2%	2
Remaining individualsnot grpmax-eligible	44.5%	2
European (non-Finnish)	43.9%	2
African / African-American	7.92%	13

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: C5
Protein: p.Val802Ile
Coding: c.2404G>A
MANE Select: NM_001735
dbSNP: rs17611
Type: single nucleotide variant
Location: chr9:121006922 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.67 · 49 PDB
Residue 802: a β-strand; a disulfide bond; a UniProt-annotated variant site (in c5d); a UniProt-annotated variant site (in)

Full C5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C5 c.2257+1G>A Likely pathogenic ★★ same type
C5 c.4679-2A>G Likely pathogenic ★★ same type
C5 p.Arg1476Ter Pathogenic/Likely pathogenic ★★ same type
C5 p.Gln19Ter Pathogenic ★★ same type
C5 p.Glu1437Ter Pathogenic/Likely pathogenic ★★ same type
C5 p.Trp469Ter Pathogenic/Likely pathogenic ★★ same type
C5 c.2059+3A>G Uncertain significance ★★ same type
C5 c.3391-13T>A Uncertain significance ★★ 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/c5-p-val802ile (accessed [today's date]).

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