Is CFH p.Asn1029Asp (c.3085A>G) pathogenic?

CFH p.Asn1029Asp (c.3085A>G) is classified Uncertain significance in CFH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). AlphaMissense: likely benign (0.1212); Ultra-rare (popmax 0.033%, mid).

How common is CFH p.Asn1029Asp (c.3085A>G) in the general population?

CFH p.Asn1029Asp (c.3085A>G) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about CFH p.Asn1029Asp (c.3085A>G)?

AlphaMissense predicts likely benign (score 0.1212) — an in-silico prediction, not a clinical call.

CFH p.Asn1029Asp

c.3085A>G · VCV3611072

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1212 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1212	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -7.43	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 -2.1	GERP -3.7
Regional constraint	o/e 1.01	unconstrained · MANE · 53 kb · p 0.76 · regional, not allelic
Overall
CADD	1.308	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000205% 3/1,461,866 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0016%	62,512

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: CFH
Protein: p.Asn1029Asp
Coding: c.3085A>G
MANE Select: NM_000186
Type: single nucleotide variant
Location: chr1:196742003 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 1029: the sushi 17 domain; a disulfide bond

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

Similar variants

CFH p.Asn1029= Likely benign ★ same residue
CFH c.1337-2A>G Likely pathogenic ★★ same type
CFH c.1520-1G>A Pathogenic/Likely pathogenic ★★ same type
CFH c.2236+1G>C Likely pathogenic ★★ same type
CFH c.3493+1G>A Pathogenic/Likely pathogenic ★★ same type
CFH c.350+1G>T Pathogenic/Likely pathogenic ★★ same type
CFH c.619+1G>A Pathogenic/Likely pathogenic ★★ same type
CFH p.Arg1215Leu Likely pathogenic ★★ ⚠ 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/cfh-p-asn1029asp (accessed [today's date]).

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