Is CFHR3 p.Val235= (c.705C>T) pathogenic?

CFHR3 p.Val235= (c.705C>T) is classified Likely benign in CFHR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-28). Ultra-rare (popmax 0.019%, afr).

How common is CFHR3 p.Val235= (c.705C>T) in the general population?

CFHR3 p.Val235= (c.705C>T) is ultra-rare (popmax 0.019%, afr) (gnomAD).

CFHR3 p.Val235=

c.705C>T · VCV4683940

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.019%, afr)

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 -15	GERP -3.6
Overall
CADD	2.723	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.019% African / African-American · 8/42,166 alleles

Filtering AF 0.00942% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00686%

Overall 0.00175% 24/1,373,946 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.019%	5,271
East Asian	0.0053%	18,879
Remaining individualsnot grpmax-eligible	0.00377%	26,544
Admixed American	0.00207%	48,248
European (non-Finnish)	0.00107%	93,709

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: CFHR3
Protein: p.Val235=
Coding: c.705C>T
MANE Select: NM_021023
Type: single nucleotide variant
Location: chr1:196790136 (GRCh38)
Gene constraint: LOEUF 1.302 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.93
Residue 235: a disulfide bond; the sushi 4 domain

Full CFHR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFHR3 c.796+1G>A Uncertain significance ★★ same type
CFHR3 p.Arg320Gln Uncertain significance ★★ ⚠ same type
CFHR3 p.Gly119Ala Uncertain significance ★★ ⚠ same type
CFHR3 p.Ile70Thr Uncertain significance ★★ ⚠ same type
CFHR3 p.Tyr118Ter Uncertain significance ★★ same type
CFHR3 c.431-88C>T Benign ★★ same type
CFHR3 c.58+8A>G Likely benign ★★ same type
CFHR3 c.796+22T>A Benign ★★ 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/cfhr3-p-val235 (accessed [today's date]).

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