Is CFAP44 p.Ser106Pro (c.316T>C) pathogenic?

CFAP44 p.Ser106Pro (c.316T>C) is classified Uncertain significance in CFAP44 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-06). AlphaMissense: likely benign (0.0786); Rare (popmax 0.313%, mid); Associated with spermatogenic failure 20.

What condition is associated with CFAP44 p.Ser106Pro (c.316T>C)?

CFAP44 p.Ser106Pro (c.316T>C) is associated with spermatogenic failure 20 (ClinVar).

How common is CFAP44 p.Ser106Pro (c.316T>C) in the general population?

CFAP44 p.Ser106Pro (c.316T>C) is rare (popmax 0.313%, mid) (gnomAD).

What do computational predictors say about CFAP44 p.Ser106Pro (c.316T>C)?

AlphaMissense predicts likely benign (score 0.0786) — an in-silico prediction, not a clinical call.

CFAP44 p.Ser106Pro

c.316T>C · rs749618390 · VCV1030243

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0786 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.313%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

spermatogenic failure 20

Computational evidence

Protein change
AlphaMissense	0.0786	likely benign
REVEL	0.002	strongly benign-leaning
SaProt	LLR -4.35	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 2.3	GERP -0.029, phastCons 0.94
Regional constraint	o/e 1.05	unconstrained · MANE · 7,513 bp · p 0.55 · regional, not allelic
Overall
CADD	16.28	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 0.313% Middle Eastern · 19/6,062 alleles

Filtering AF 0.205% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.171%

Overall 0.00124% 20/1,614,134 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.313%	319
European (non-Finnish)	8.47e-05%	1,179,984

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: CFAP44
Protein: p.Ser106Pro
Coding: c.316T>C
MANE Select: NM_001164496
dbSNP: rs749618390
Type: single nucleotide variant
Location: chr3:113426215 (GRCh38)
Gene constraint: LOEUF 0.697 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.87 · 1 PDB

Full CFAP44 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spermatogenic failure 20 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP44 p.Glu463Ter Pathogenic ★★ same condition
CFAP44 c.408-2A>T Likely pathogenic ★ same condition
CFAP44 c.5078-2A>G Likely pathogenic ★ same condition
CFAP44 p.Arg224Ter Likely pathogenic ★ same condition
CFAP44 p.Gly435Ter Likely pathogenic ★ same condition
CFAP44 p.Tyr546His Uncertain significance ★ ⚠ same condition
CFAP44 p.Arg1059Ter Pathogenic same condition
CFAP44 p.Leu590Gln Pathogenic same condition

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/cfap44-p-ser106pro (accessed [today's date]).

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