Is CFHR2 p.Pro247Ser (c.739C>T) pathogenic?

CFHR2 p.Pro247Ser (c.739C>T) is classified Uncertain significance in CFHR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.08); Absent from gnomAD v4.1.

How common is CFHR2 p.Pro247Ser (c.739C>T) in the general population?

CFHR2 p.Pro247Ser (c.739C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFHR2 p.Pro247Ser (c.739C>T)?

AlphaMissense predicts likely benign (score 0.08) — an in-silico prediction, not a clinical call.

CFHR2 p.Pro247Ser

c.739C>T · VCV4227322

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.08 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.08	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -7.07	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 -20	GERP -3.4
Regional constraint	o/e 1.00	unconstrained · MANE · 15 kb · p 0.97 · regional, not allelic
Overall
CADD	0.037	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFHR2
Protein: p.Pro247Ser
Coding: c.739C>T
MANE Select: NM_005666
Type: single nucleotide variant
Location: chr1:196959006 (GRCh38)
Gene constraint: LOEUF 1.498 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.90 · 4 PDB
Residue 247: the sushi 4 domain

Full CFHR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFHR2 p.Val16Ala Uncertain significance ★★ ⚠ same type
CFHR2 c.430+141T>A Benign ★★ same type
CFHR2 c.430+20C>T Benign ★★ same type
CFHR2 c.430+7G>A Benign/Likely benign ★★ same type
CFHR2 c.431-48C>A Benign ★★ same type
CFHR2 c.431-65C>T Benign ★★ same type
CFHR2 c.58+129C>G Benign ★★ same type
CFHR2 c.-65C>G 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/cfhr2-p-pro247ser (accessed [today's date]).

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