Is C5 p.Leu571Val (c.1711C>G) pathogenic?

C5 p.Leu571Val (c.1711C>G) is classified Uncertain significance in C5 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-12-11). AlphaMissense: likely benign (0.1718); Rare (popmax 0.528%, mid); Associated with C5-related disorder.

What condition is associated with C5 p.Leu571Val (c.1711C>G)?

C5 p.Leu571Val (c.1711C>G) is associated with C5-related disorder, complement component 5 deficiency (ClinVar).

How common is C5 p.Leu571Val (c.1711C>G) in the general population?

C5 p.Leu571Val (c.1711C>G) is rare (popmax 0.528%, mid) (gnomAD).

What do computational predictors say about C5 p.Leu571Val (c.1711C>G)?

AlphaMissense predicts likely benign (score 0.1718) — an in-silico prediction, not a clinical call.

C5 p.Leu571Val

c.1711C>G · rs147226792 · VCV548014

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1718 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.528%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

C5-related disorder

Computational evidence

Protein change
AlphaMissense	0.1718	likely benign
REVEL	0.244	benign-leaning
SaProt	LLR -9.78	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 4	GERP 1, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 98 kb · p 1.2e-09 · regional, not allelic
Overall
CADD	23.6	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 0.528% Middle Eastern · 32/6,062 alleles

Filtering AF 0.384% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.335%

Overall 0.0162% 261/1,612,542 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.528%	189
South Asian	0.0824%	1,214
Remaining individualsnot grpmax-eligible	0.0384%	2,602
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,397
Admixed American	0.01%	10,003
European (non-Finnish)	0.00992%	10,076
East Asian	0.00446%	22,433
African / African-American	0.00133%	75,026

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.Leu571Val
Coding: c.1711C>G
MANE Select: NM_001735
dbSNP: rs147226792
Type: single nucleotide variant
Location: chr9:121017648 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.67 · 49 PDB
Residue 571: a β-strand; a disulfide bond; a UniProt-annotated variant site (in c5d)

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

Disease context

C5-related disorder

Also linked: complement component 5 deficiency

Similar variants

C5 p.Leu571= Likely benign ★ same residue
C5 c.2257+1G>A Likely pathogenic ★★ same condition
C5 c.4679-2A>G Likely pathogenic ★★ same condition
C5 p.Arg1476Ter Pathogenic/Likely pathogenic ★★ same condition
C5 p.Gln19Ter Pathogenic ★★ same condition
C5 p.Glu1437Ter Pathogenic/Likely pathogenic ★★ same condition
C5 p.Trp469Ter Pathogenic/Likely pathogenic ★★ same condition
C5 c.2059+3A>G 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/c5-p-leu571val (accessed [today's date]).

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