Is CFHR4 p.Pro510= (c.1530A>T) pathogenic?

CFHR4 p.Pro510= (c.1530A>T) is classified Benign/Likely benign in CFHR4 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-21). Common (popmax 33.1%, eas) — too common for a highly-penetrant pathogenic allele.

CFHR4 p.Pro510=

Q: How common is CFHR4 p.Pro510= (c.1530A>T) in the general population?

CFHR4 p.Pro510= (c.1530A>T) is common (popmax 33.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1530A>T · rs150845796 · VCV769252

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 33.1%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.3	GERP -3.6
Overall
CADD	2.75	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 33.1% East Asian · 12,567/37,998 alleles

Filtering AF 32.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 32.4%

Overall 14.3% 215,444/1,504,516 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	33.1%	3
Admixed American	24.1%	4
African / African-American	19%	5
Amishnot grpmax-eligible	15.3%	7
Remaining individualsnot grpmax-eligible	14.7%	7
European (non-Finnish)	13.5%	7
Middle Eastern	12.9%	8
Finnishnot grpmax-eligible	11.1%	9
Ashkenazi Jewishnot grpmax-eligible	11%	9
South Asian	10.5%	10

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: CFHR4
Protein: p.Pro510=
Coding: c.1530A>T
MANE Select: NM_001201550
dbSNP: rs150845796
Type: single nucleotide variant
Location: chr1:196915128 (GRCh38)
Gene constraint: LOEUF 1.204 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.75
Residue 510: a disulfide bond; the sushi 8 domain

Full CFHR4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFHR4 p.Pro510Ser Uncertain significance ★ ⚠ same residue
CFHR4 p.Pro510Thr Uncertain significance ★ ⚠ same residue
CFHR4 p.Ala159Val Uncertain significance ★★ ⚠ same type
CFHR4 p.Arg40His Uncertain significance ★★ ⚠ same type
CFHR4 p.Ile318Thr Uncertain significance ★★ ⚠ same type
CFHR4 p.Ser199Tyr Uncertain significance ★★ ⚠ same type
CFHR4 p.Ser507Leu Uncertain significance ★★ ⚠ same type
CFHR4 p.Trp68Ter 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/cfhr4-p-pro510 (accessed [today's date]).

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