Is CFAP61 p.Arg382Ser (c.1146G>C) pathogenic?

CFAP61 p.Arg382Ser (c.1146G>C) is classified Likely benign in CFAP61 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-01). AlphaMissense: likely benign (0.2237); Rare (popmax 0.974%, mid).

How common is CFAP61 p.Arg382Ser (c.1146G>C) in the general population?

CFAP61 p.Arg382Ser (c.1146G>C) is rare (popmax 0.974%, mid) (gnomAD).

What do computational predictors say about CFAP61 p.Arg382Ser (c.1146G>C)?

AlphaMissense predicts likely benign (score 0.2237) — an in-silico prediction, not a clinical call.

CFAP61 p.Arg382Ser

c.1146G>C · rs116315783 · VCV2652231

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2237 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.974%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2237	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -7.63	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 1.8	GERP -3.9, phastCons 0.94
Regional constraint	o/e 0.97	unconstrained · MANE · 304 kb · p 0.21 · regional, not allelic
Overall
CADD	9.568	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 0.974% Middle Eastern · 59/6,058 alleles

Filtering AF 0.775% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.703%

Overall 0.298% 4,804/1,614,040 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	5.48%	18
Middle Easterngrpmax	0.974%	103
European (non-Finnish)	0.356%	281
Ashkenazi Jewishnot grpmax-eligible	0.291%	344
Remaining individualsnot grpmax-eligible	0.266%	377
Admixed American	0.205%	488
African / African-American	0.068%	1,471
South Asian	0.056%	1,786
Finnishnot grpmax-eligible	0.0187%	5,335

Amish 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.Arg382Ser
Coding: c.1146G>C
MANE Select: NM_015585
dbSNP: rs116315783
Type: single nucleotide variant
Location: chr20:20164169 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.86 · 1 PDB
Residue 382: 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-arg382ser (accessed [today's date]).

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