Is CFHR5 p.Pro453Ser (c.1357C>T) pathogenic?

CFHR5 p.Pro453Ser (c.1357C>T) is classified Likely benign in CFHR5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-05-28). AlphaMissense: likely benign (0.2339); Rare (popmax 0.285%, eas); Associated with Inborn genetic diseases.

What condition is associated with CFHR5 p.Pro453Ser (c.1357C>T)?

CFHR5 p.Pro453Ser (c.1357C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CFHR5 p.Pro453Ser (c.1357C>T) in the general population?

CFHR5 p.Pro453Ser (c.1357C>T) is rare (popmax 0.285%, eas) (gnomAD).

What do computational predictors say about CFHR5 p.Pro453Ser (c.1357C>T)?

AlphaMissense predicts likely benign (score 0.2339) — an in-silico prediction, not a clinical call.

CFHR5 p.Pro453Ser

c.1357C>T · rs184883943 · VCV3143825

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2339 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.285%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2339	likely benign
REVEL	0.322	indeterminate
SaProt	LLR -13.31	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.8, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 31 kb · p 0.00015 · regional, not allelic
Overall
CADD	20.9	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 0.285% East Asian · 128/44,864 alleles

Filtering AF 0.245% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.23%

Overall 0.00812% 131/1,613,578 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.285%	350
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	8.48e-05%	1,179,592

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: CFHR5
Protein: p.Pro453Ser
Coding: c.1357C>T
MANE Select: NM_030787
dbSNP: rs184883943
Type: single nucleotide variant
Location: chr1:197004687 (GRCh38)
Gene constraint: LOEUF 1.466 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.76
Residue 453: a disulfide bond; the sushi 8 domain

Full CFHR5 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

CFHR5 p.Pro453Ala Uncertain significance ★ ⚠ same residue
CFHR5 p.Arg132Gln Uncertain significance ★★ ⚠ same condition
CFHR5 p.Arg132Trp Uncertain significance ★★ ⚠ same condition
CFHR5 p.Arg356Cys Uncertain significance ★★ ⚠ same condition
CFHR5 p.Arg364Ser Uncertain significance ★★ ⚠ same condition
CFHR5 p.Asn126His Uncertain significance ★★ ⚠ same condition
CFHR5 p.Asn230Asp Uncertain significance ★★ ⚠ same condition
CFHR5 p.Asp24Ala 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/cfhr5-p-pro453ser (accessed [today's date]).

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