Is CFAP61 p.Arg800Trp (c.2398C>T) pathogenic?

CFAP61 p.Arg800Trp (c.2398C>T) is classified Uncertain significance in CFAP61 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-27). AlphaMissense: likely benign (0.0956); Ultra-rare (popmax 0.0329%, mid).

How common is CFAP61 p.Arg800Trp (c.2398C>T) in the general population?

CFAP61 p.Arg800Trp (c.2398C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about CFAP61 p.Arg800Trp (c.2398C>T)?

AlphaMissense predicts likely benign (score 0.0956) — an in-silico prediction, not a clinical call.

CFAP61 p.Arg800Trp

c.2398C>T · VCV4001589

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0956 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0956	likely benign
REVEL	0.129	moderately benign-leaning
SaProt	LLR -3.24	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 1.1	GERP -0.14
Regional constraint	o/e 0.97	unconstrained · MANE · 304 kb · p 0.21 · regional, not allelic
Overall
CADD	19.71	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 0.0329% Middle Eastern · 2/6,080 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.000744% 12/1,613,636 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,040
African / African-American	0.00267%	37,428
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)	0.000593%	168,538

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: CFAP61
Protein: p.Arg800Trp
Coding: c.2398C>T
MANE Select: NM_015585
Type: single nucleotide variant
Location: chr20:20263025 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.86 · 1 PDB
Residue 800: a UniProt-annotated variant site (in spgf84; pathogenic; no protein detected in patient sperm)

Full CFAP61 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP61 p.Arg800Gln Likely benign ★ same residue
CFAP61 p.Arg552Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
CFAP61 c.3125-1G>C Likely pathogenic ★ same type
CFAP61 p.Arg283Ter Pathogenic ★ same type
CFAP61 p.Val755Ala Likely pathogenic ★ ⚠ same type
CFAP61 p.Ala1026Asp Uncertain significance ★ ⚠ same type
CFAP61 p.Ala1081Gly Uncertain significance ★ ⚠ same type
CFAP61 p.Ala1081Ser 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/cfap61-p-arg800trp (accessed [today's date]).

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