Is CFHR1 p.Thr196= (c.588A>G) pathogenic?

CFHR1 p.Thr196= (c.588A>G) is classified Benign in CFHR1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-26). Common (popmax 35.7%, eas) — too common for a highly-penetrant pathogenic allele.

CFHR1 p.Thr196=

Q: How common is CFHR1 p.Thr196= (c.588A>G) in the general population?

CFHR1 p.Thr196= (c.588A>G) is common (popmax 35.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.588A>G · rs3201739 · VCV1283250

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 35.7%, eas) — 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 -1.7	GERP 0.33
Overall
CADD	7.445	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 35.7% East Asian · 9,447/26,438 alleles

Filtering AF 35.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 34.9%

Overall 14.6% 137,061/937,300 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	35.7%	3
Admixed American	27.8%	4
African / African-American	25.6%	4
Ashkenazi Jewishnot grpmax-eligible	25.4%	4
South Asian	18.9%	5
Remaining individualsnot grpmax-eligible	16.7%	6
Finnishnot grpmax-eligible	16.4%	6
European (non-Finnish)	11.8%	8
Middle Eastern	11%	9
Amishnot grpmax-eligible	10.4%	10

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.Thr196=
Coding: c.588A>G
MANE Select: NM_002113
dbSNP: rs3201739
Type: single nucleotide variant
Location: chr1:196828227 (GRCh38)
Gene constraint: LOEUF 1.208 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.21 · 2 PDB
Residue 196: a disulfide bond; the sushi 3 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-thr196 (accessed [today's date]).

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