Is CFHR2 p.Val92Glu (c.275T>A) pathogenic?

CFHR2 p.Val92Glu (c.275T>A) is classified Likely benign in CFHR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-13). AlphaMissense: likely pathogenic (0.6488); Rare (popmax 0.36%, sas).

How common is CFHR2 p.Val92Glu (c.275T>A) in the general population?

CFHR2 p.Val92Glu (c.275T>A) is rare (popmax 0.36%, sas) (gnomAD).

What do computational predictors say about CFHR2 p.Val92Glu (c.275T>A)?

AlphaMissense predicts likely pathogenic (score 0.6488) — an in-silico prediction, not a clinical call.

CFHR2 p.Val92Glu

c.275T>A · VCV4684016

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6488 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.36%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6488	likely pathogenic
REVEL	0.396	indeterminate
SaProt	LLR -13.55	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 15 kb · p 0.97 · regional, not allelic
Overall
CADD	24.5	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 0.36% South Asian · 328/91,056 alleles

Filtering AF 0.328% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.316%

Overall 0.0218% 351/1,613,666 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.36%	278
Remaining individualsnot grpmax-eligible	0.032%	3,123
Middle Eastern	0.0171%	5,846
African / African-American	0.00133%	75,046
European (non-Finnish)	8.48e-05%	1,179,856

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: CFHR2
Protein: p.Val92Glu
Coding: c.275T>A
MANE Select: NM_005666
Type: single nucleotide variant
Location: chr1:196950873 (GRCh38)
Gene constraint: LOEUF 1.498 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.90 · 4 PDB
Residue 92: the sushi 2 domain; a disulfide bond

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-val92glu (accessed [today's date]).

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