Is CFH p.Lys1004Glu (c.3010A>G) pathogenic?

CFH p.Lys1004Glu (c.3010A>G) is classified Uncertain significance in CFH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-17). AlphaMissense: likely benign (0.0918); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CFH p.Lys1004Glu (c.3010A>G)?

CFH p.Lys1004Glu (c.3010A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CFH p.Lys1004Glu (c.3010A>G) in the general population?

CFH p.Lys1004Glu (c.3010A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFH p.Lys1004Glu (c.3010A>G)?

AlphaMissense predicts likely benign (score 0.0918) — an in-silico prediction, not a clinical call.

CFH p.Lys1004Glu

c.3010A>G · rs773493265 · VCV2793370

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0918 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0918	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -1.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8	GERP -3.7
Regional constraint	o/e 1.01	unconstrained · MANE · 53 kb · p 0.76 · regional, not allelic
Overall
CADD	0.114	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: CFH
Protein: p.Lys1004Glu
Coding: c.3010A>G
MANE Select: NM_000186
dbSNP: rs773493265
Type: single nucleotide variant
Location: chr1:196741928 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 1004: the sushi 17 domain; a disulfide bond

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFH p.Ala421Thr Uncertain significance ★★ ⚠ same condition
CFH p.Arg53Leu Uncertain significance ★★ ⚠ same condition
CFH p.Asn1050Ile Uncertain significance ★★ ⚠ same condition
CFH p.Asn660His Uncertain significance ★★ ⚠ same condition
CFH p.Asn75His Uncertain significance ★★ ⚠ same condition
CFH p.Asp276Glu Uncertain significance ★★ ⚠ same condition
CFH p.Asp855Asn Uncertain significance ★★ ⚠ same condition
CFH p.Asp947His Uncertain significance ★★ ⚠ same condition

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/cfh-p-lys1004glu (accessed [today's date]).

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