Is CFAP44 p.Ser291Leu (c.872C>T) pathogenic?

CFAP44 p.Ser291Leu (c.872C>T) is classified Uncertain significance in CFAP44 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-18). AlphaMissense: ambiguous (0.3662); Ultra-rare (popmax 0.0104%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CFAP44 p.Ser291Leu (c.872C>T)?

CFAP44 p.Ser291Leu (c.872C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CFAP44 p.Ser291Leu (c.872C>T) in the general population?

CFAP44 p.Ser291Leu (c.872C>T) is ultra-rare (popmax 0.0104%, nfe) (gnomAD).

What do computational predictors say about CFAP44 p.Ser291Leu (c.872C>T)?

AlphaMissense predicts ambiguous (score 0.3662) — an in-silico prediction, not a clinical call.

CFAP44 p.Ser291Leu

c.872C>T · rs371652370 · VCV2351106

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3662 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0104%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3662	ambiguous
REVEL	0.137	moderately benign-leaning
SaProt	LLR -12.44	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.22	donor loss, 18 bp away · masked 0 · deltas
Pangolin	Δ0.26	loss · gain 0.07 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 129 kb · p 0.0018 · regional, not allelic
Overall
CADD	23.4	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 0.0104% European (non-Finnish) · 122/1,177,830 alleles

Filtering AF 0.00886% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0083%

Overall 0.0082% 132/1,609,500 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0104%	9,654
Remaining individualsnot grpmax-eligible	0.00643%	15,559
East Asian	0.00448%	22,316
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,478
Admixed American	0.00335%	29,863
African / African-American	0.00134%	74,400

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.Ser291Leu
Coding: c.872C>T
MANE Select: NM_001164496
dbSNP: rs371652370
Type: single nucleotide variant
Location: chr3:113409124 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP44 p.Ser291Thr Uncertain significance ★ ⚠ same residue
CFAP44 p.Ala161Gly Uncertain significance ★ ⚠ same condition
CFAP44 p.Ala712Val Uncertain significance ★ ⚠ same condition
CFAP44 p.Arg495Gln Uncertain significance ★ ⚠ same condition
CFAP44 p.Arg522Gln Uncertain significance ★ ⚠ same condition
CFAP44 p.Arg557Gln Uncertain significance ★ ⚠ same condition
CFAP44 p.Arg585Cys Uncertain significance ★ ⚠ same condition
CFAP44 p.Arg606Met Uncertain significance ★ ⚠ 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-ser291leu (accessed [today's date]).

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