Is CFAP91 p.His53= (c.159T>C) pathogenic?

CFAP91 p.His53= (c.159T>C) is classified Likely benign in CFAP91 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-01). Ultra-rare (popmax 0.0135%, nfe).

How common is CFAP91 p.His53= (c.159T>C) in the general population?

CFAP91 p.His53= (c.159T>C) is ultra-rare (popmax 0.0135%, nfe) (gnomAD).

CFAP91 p.His53=

c.159T>C · rs368173878 · VCV3025363

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, nfe)

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 -0.11	GERP -3.3
Overall
CADD	5.513	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0135% European (non-Finnish) · 159/1,179,824 alleles

Filtering AF 0.0117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0111%

Overall 0.0112% 180/1,613,382 alleles · ultra-rare exomes 164/1,461,712 · genomes 16/151,670 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0156%	6,397
Remaining individualsnot grpmax-eligible	0.0144%	6,941
European (non-Finnish)grpmax	0.0135%	7,420
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
East Asian	0.00223%	44,888

Finnish 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: CFAP91
Protein: p.His53=
Coding: c.159T>C
MANE Select: NM_033364
dbSNP: rs368173878
Type: single nucleotide variant
Location: chr3:119706843 (GRCh38)
Gene constraint: LOEUF 1.129 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.20 · 1 PDB

Full CFAP91 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP91 p.His53Tyr Uncertain significance ★ ⚠ same residue
CFAP91 c.359+1G>A Likely pathogenic ★ same type
CFAP91 p.Gln545Ter Likely pathogenic ★ same type
CFAP91 c.501-3T>C Uncertain significance ★ same type
CFAP91 p.Ala249Asp Uncertain significance ★ ⚠ same type
CFAP91 p.Ala256Thr Uncertain significance ★ ⚠ same type
CFAP91 p.Ala449Val Uncertain significance ★ ⚠ same type
CFAP91 p.Ala598Ser Uncertain significance ★ ⚠ 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/cfap91-p-his53 (accessed [today's date]).

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