Is CPSF4L p.Phe44Val (c.130T>G) pathogenic?

CPSF4L p.Phe44Val (c.130T>G) is classified Uncertain significance in CPSF4L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-12). AlphaMissense: likely benign (0.3277); Very rare (popmax 0.0041%, nfe).

How common is CPSF4L p.Phe44Val (c.130T>G) in the general population?

CPSF4L p.Phe44Val (c.130T>G) is very rare (popmax 0.0041%, nfe) (gnomAD).

What do computational predictors say about CPSF4L p.Phe44Val (c.130T>G)?

AlphaMissense predicts likely benign (score 0.3277) — an in-silico prediction, not a clinical call.

CPSF4L p.Phe44Val

c.130T>G · rs779998731 · VCV2400497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3277 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0041%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3277	likely benign
REVEL	0.26	benign-leaning
SaProt	LLR -12.45	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP -0.44, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.47 · regional, not allelic
Overall
CADD	20.8	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 0.0041% European (non-Finnish) · 47/1,146,360 alleles

Filtering AF 0.00316% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00283%

Overall 0.00316% 49/1,550,512 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0041%	24,391
Finnishnot grpmax-eligible	0.00167%	59,706
Remaining individualsnot grpmax-eligible	0.00167%	60,050

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: CPSF4L
Protein: p.Phe44Val
Coding: c.130T>G
MANE Select: NM_001129885
dbSNP: rs779998731
Type: single nucleotide variant
Location: chr17:73260957 (GRCh38)
Gene constraint: LOEUF 1.452 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.79

Full CPSF4L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPSF4L p.Arg145Lys Uncertain significance ★ ⚠ same type
CPSF4L p.Arg58Gln Uncertain significance ★ ⚠ same type
CPSF4L p.Arg61Gln Uncertain significance ★ ⚠ same type
CPSF4L p.Arg73Gln Uncertain significance ★ ⚠ same type
CPSF4L p.Asp18Val Uncertain significance ★ ⚠ same type
CPSF4L p.Gln163Pro Uncertain significance ★ ⚠ same type
CPSF4L p.Glu50Ala Uncertain significance ★ ⚠ same type
CPSF4L p.Glu63Ala 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/cpsf4l-p-phe44val (accessed [today's date]).

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