Is CFHR1 p.Ter331IleextTer? (c.991_*1del) pathogenic?

CFHR1 p.Ter331IleextTer? (c.9911del) is classified Likely benign in CFHR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-29). Very rare (popmax 0.00874%, sas).

How common is CFHR1 p.Ter331IleextTer? (c.991_*1del) in the general population?

CFHR1 p.Ter331IleextTer? (c.991_*1del) is very rare (popmax 0.00874%, sas) (gnomAD).

CFHR1 p.Ter331IleextTer?

c.991_*1del · rs747899966 · VCV3025933

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00874%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.47	GERP -3.7
Overall
CADD	16.65	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00874% South Asian · 7/80,120 alleles

Filtering AF 0.00402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00283%

Overall 0.00447% 68/1,522,160 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0102%	9,805
South Asiangrpmax	0.00874%	11,446
Admixed American	0.00862%	11,601
Finnishnot grpmax-eligible	0.00482%	20,733
European (non-Finnish)	0.00391%	25,591
African / African-American	0.0034%	29,385
East Asian	0.00224%	44,598

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ter331IleextTer?
Coding: c.991_*1del
MANE Select: NM_002113
dbSNP: rs747899966
Type: Deletion
Location: chr1:196831994 (GRCh38)
Gene constraint: LOEUF 1.208 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.21 · 2 PDB

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

Similar variants

CFHR1 p.Ter331Trp Conflicting classifications of pathogenicity ★ same residue
CFHR1 p.Asp35fs Uncertain significance ★ same type
CFHR1 p.Ser6_Val7insTer Conflicting classifications of pathogenicity ★ 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-ter331ileextter (accessed [today's date]).

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