Is CFHR1 p.Arg314= (c.942A>T) pathogenic?

CFHR1 p.Arg314= (c.942A>T) is classified Benign/Likely benign in CFHR1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2024-11-26). Common (popmax 51.9%, amr) — too common for a highly-penetrant pathogenic allele.

CFHR1 p.Arg314=

Q: How common is CFHR1 p.Arg314= (c.942A>T) in the general population?

CFHR1 p.Arg314= (c.942A>T) is common (popmax 51.9%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.942A>T · rs414628 · VCV1233842

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 51.9%, amr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.94	GERP -3
Overall
CADD	2.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 51.9% Admixed American · 29,990/57,788 alleles

Filtering AF 51.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 51.2%

Overall 42.2% 642,671/1,521,694 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	51.9%	2
East Asian	51.5%	2
Ashkenazi Jewishnot grpmax-eligible	51.2%	2
Remaining individualsnot grpmax-eligible	43.1%	2
South Asian	42.1%	2
European (non-Finnish)	41.6%	2
Middle Eastern	40.5%	2
Finnishnot grpmax-eligible	38.9%	3
African / African-American	37.1%	3
Amishnot grpmax-eligible	17.7%	6

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: CFHR1
Protein: p.Arg314=
Coding: c.942A>T
MANE Select: NM_002113
dbSNP: rs414628
Type: single nucleotide variant
Location: chr1:196831948 (GRCh38)
Gene constraint: LOEUF 1.208 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.21 · 2 PDB
Residue 314: a disulfide bond; a β-strand; the sushi 5 domain

Full CFHR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFHR1 p.Asp218Asn Uncertain significance ★★ ⚠ same type
CFHR1 p.Gln44Ter Uncertain significance ★★ same type
CFHR1 p.Ile214Asn Uncertain significance ★★ ⚠ same type
CFHR1 p.Ile70Val Uncertain significance ★★ ⚠ same type
CFHR1 p.Pro223Leu Uncertain significance ★★ ⚠ same type
CFHR1 p.Tyr304Cys Uncertain significance ★★ ⚠ same type
CFHR1 c.253+108G>C Benign ★★ same type
CFHR1 c.253+213G>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/cfhr1-p-arg314 (accessed [today's date]).

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