Is CFHR3 p.Ile151Val (c.451A>G) pathogenic?

CFHR3 p.Ile151Val (c.451A>G) is classified Uncertain significance in CFHR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely benign (0.0963); Ultra-rare (popmax 0.0463%, afr).

How common is CFHR3 p.Ile151Val (c.451A>G) in the general population?

CFHR3 p.Ile151Val (c.451A>G) is ultra-rare (popmax 0.0463%, afr) (gnomAD).

What do computational predictors say about CFHR3 p.Ile151Val (c.451A>G)?

AlphaMissense predicts likely benign (score 0.0963) — an in-silico prediction, not a clinical call.

CFHR3 p.Ile151Val

c.451A>G · VCV4653045

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0963 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0463%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0963	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -8.81	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 -0.45	GERP -2.7
Regional constraint	o/e 0.72	unconstrained · MANE · 15 kb · p 1.1e-05 · regional, not allelic
Overall
CADD	0.134	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 0.0463% African / African-American · 26/56,184 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0278%

Overall 0.00194% 28/1,441,244 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0463%	2,161
Remaining individualsnot grpmax-eligible	0.00363%	27,579

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.Ile151Val
Coding: c.451A>G
MANE Select: NM_021023
Type: single nucleotide variant
Location: chr1:196788236 (GRCh38)
Gene constraint: LOEUF 1.302 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.93
Residue 151: a disulfide bond; the sushi 3 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-ile151val (accessed [today's date]).

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