Is CFAP61 p.Ser688Phe (c.2063C>T) pathogenic?

CFAP61 p.Ser688Phe (c.2063C>T) is classified Uncertain significance in CFAP61 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: ambiguous (0.4687); Very rare (popmax 0.000171%, nfe).

How common is CFAP61 p.Ser688Phe (c.2063C>T) in the general population?

CFAP61 p.Ser688Phe (c.2063C>T) is very rare (popmax 0.000171%, nfe) (gnomAD).

What do computational predictors say about CFAP61 p.Ser688Phe (c.2063C>T)?

AlphaMissense predicts ambiguous (score 0.4687) — an in-silico prediction, not a clinical call.

CFAP61 p.Ser688Phe

c.2063C>T · VCV4001605

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4687 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4687	ambiguous
REVEL	0.31	indeterminate
SaProt	LLR -6.20	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 304 kb · p 0.21 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000171% European (non-Finnish) · 2/1,166,506 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000125% 2/1,595,062 alleles · very rare exomes 2/1,442,814 · genomes 0/152,248 · joint denominator

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.Ser688Phe
Coding: c.2063C>T
MANE Select: NM_015585
Type: single nucleotide variant
Location: chr20:20246119 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.86 · 1 PDB
Residue 688: 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.Ser688Pro Uncertain significance ★ ⚠ 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-ser688phe (accessed [today's date]).

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