Is C5 p.Pro191Leu (c.572C>T) pathogenic?

C5 p.Pro191Leu (c.572C>T) is classified Uncertain significance in C5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-04). AlphaMissense: likely benign (0.2879); Ultra-rare (popmax 0.0246%, sas); Associated with complement component 5 deficiency.

What condition is associated with C5 p.Pro191Leu (c.572C>T)?

C5 p.Pro191Leu (c.572C>T) is associated with complement component 5 deficiency (ClinVar).

How common is C5 p.Pro191Leu (c.572C>T) in the general population?

C5 p.Pro191Leu (c.572C>T) is ultra-rare (popmax 0.0246%, sas) (gnomAD).

What do computational predictors say about C5 p.Pro191Leu (c.572C>T)?

AlphaMissense predicts likely benign (score 0.2879) — an in-silico prediction, not a clinical call.

C5 p.Pro191Leu

Q: How is Immunodeficiency due to a late component of complement deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.572C>T · rs200524363 · VCV1408015

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2879 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0246%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

complement component 5 deficiency

Computational evidence

Protein change
AlphaMissense	0.2879	likely benign
REVEL	0.65	pathogenic-leaning
SaProt	LLR -11.56	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 98 kb · p 1.2e-09 · regional, not allelic
Overall
CADD	33.0	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 0.0246% South Asian · 22/89,588 alleles

Filtering AF 0.0165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.014%

Overall 0.00329% 51/1,552,022 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0246%	4,072
Middle Eastern	0.0168%	5,944
Admixed American	0.00502%	19,929
Remaining individualsnot grpmax-eligible	0.00496%	20,164
East Asian	0.00225%	44,506
European (non-Finnish)	0.00187%	53,562

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.Pro191Leu
Coding: c.572C>T
MANE Select: NM_001735
dbSNP: rs200524363
Type: single nucleotide variant
Location: chr9:121034815 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.67 · 49 PDB
Residue 191: a UniProt-annotated variant site (in c5d)

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

Disease context

complement component 5 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Immunodeficiency due to a late component of complement deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

C5 p.Pro191= 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.Trp469Ter Pathogenic/Likely pathogenic ★★ same condition
C5 c.2059+3A>G Uncertain significance ★★ same condition
C5 c.4081-6A>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-pro191leu (accessed [today's date]).

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