Is CFAP44 p.Val1370Ile (c.4108G>A) pathogenic?

CFAP44 p.Val1370Ile (c.4108G>A) is classified Uncertain significance in CFAP44 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-01). AlphaMissense: likely benign (0.071); Rare (popmax 0.419%, mid).

How common is CFAP44 p.Val1370Ile (c.4108G>A) in the general population?

CFAP44 p.Val1370Ile (c.4108G>A) is rare (popmax 0.419%, mid) (gnomAD).

What do computational predictors say about CFAP44 p.Val1370Ile (c.4108G>A)?

AlphaMissense predicts likely benign (score 0.071) — an in-silico prediction, not a clinical call.

CFAP44 p.Val1370Ile

c.4108G>A · rs748434148 · VCV2654042

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.071 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.419%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.071	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -4.57	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 -0.018	GERP -4.7, phastCons 0.001
Regional constraint	o/e 0.93	unconstrained · MANE · 129 kb · p 0.0018 · regional, not allelic
Overall
CADD	0.677	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 0.419% Middle Eastern · 25/5,972 alleles

Filtering AF 0.291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.249%

Overall 0.00998% 153/1,532,490 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.419%	239
Ashkenazi Jewishnot grpmax-eligible	0.0353%	2,837
Remaining individualsnot grpmax-eligible	0.02%	5,001
Admixed American	0.0138%	7,260
European (non-Finnish)	0.00769%	12,998
African / African-American	0.00684%	14,614
South Asian	0.00482%	20,765
East Asian	0.00245%	40,824
Finnishnot grpmax-eligible	0.00219%	45,652

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.Val1370Ile
Coding: c.4108G>A
MANE Select: NM_001164496
dbSNP: rs748434148
Type: single nucleotide variant
Location: chr3:113330176 (GRCh38)
Gene constraint: LOEUF 0.697 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.87 · 1 PDB
Residue 1370: a UniProt-annotated variant site (in spgf20)

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

Similar variants

CFAP44 p.Glu463Ter Pathogenic ★★ same type
CFAP44 c.4759-3C>T Benign ★★ same type
CFAP44 p.Ala157= Benign ★★ same type
CFAP44 p.Ala486Val Likely benign ★★ ⚠ same type
CFAP44 p.Arg1059Gln Benign ★★ same type
CFAP44 p.Arg1495Trp Benign ★★ ⚠ same type
CFAP44 p.Arg1651Trp Benign/Likely benign ★★ ⚠ same type
CFAP44 p.Arg1806= Benign/Likely benign ★★ 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/cfap44-p-val1370ile (accessed [today's date]).

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