Is CFAP61 p.Asp643Tyr (c.1927G>T) pathogenic?

CFAP61 p.Asp643Tyr (c.1927G>T) is classified Uncertain significance in CFAP61 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: likely benign (0.1302); Very rare (popmax 0.00133%, afr).

How common is CFAP61 p.Asp643Tyr (c.1927G>T) in the general population?

CFAP61 p.Asp643Tyr (c.1927G>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CFAP61 p.Asp643Tyr (c.1927G>T)?

AlphaMissense predicts likely benign (score 0.1302) — an in-silico prediction, not a clinical call.

CFAP61 p.Asp643Tyr

c.1927G>T · VCV3491405

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1302 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1302	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -5.22	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 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 304 kb · p 0.21 · regional, not allelic
Overall
CADD	28.2	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 0.00133% African / African-American · 1/75,056 alleles

Overall 0.000205% 3/1,461,606 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00157%	63,826
African / African-Americangrpmax	0.00133%	75,056
European (non-Finnish)	8.47e-05%	1,180,008

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: CFAP61
Protein: p.Asp643Tyr
Coding: c.1927G>T
MANE Select: NM_015585
Type: single nucleotide variant
Location: chr20:20199897 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.86 · 1 PDB
Residue 643: 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.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
CFAP61 p.Ala1232Val 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-asp643tyr (accessed [today's date]).

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