Is NTF4 p.Pro53Ser (c.157C>T) pathogenic?

NTF4 p.Pro53Ser (c.157C>T) is classified Uncertain significance in NTF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-05). AlphaMissense: ambiguous (0.5019); Very rare (popmax 0.00192%, nfe); Associated with Inborn genetic diseases.

What condition is associated with NTF4 p.Pro53Ser (c.157C>T)?

NTF4 p.Pro53Ser (c.157C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NTF4 p.Pro53Ser (c.157C>T) in the general population?

NTF4 p.Pro53Ser (c.157C>T) is very rare (popmax 0.00192%, nfe) (gnomAD).

What do computational predictors say about NTF4 p.Pro53Ser (c.157C>T)?

AlphaMissense predicts ambiguous (score 0.5019) — an in-silico prediction, not a clinical call.

NTF4 p.Pro53Ser

c.157C>T · rs1017274820 · VCV2332650

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5019 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00192%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5019	ambiguous
REVEL	0.488	indeterminate
SaProt	LLR -9.76	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 629 bp · p 0.054 · regional, not allelic
Overall
CADD	25.2	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 0.00192% European (non-Finnish) · 22/1,147,138 alleles

Filtering AF 0.00126% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00107%

Overall 0.00142% 22/1,550,684 alleles · very rare exomes 22/1,398,420 · genomes 0/152,264 · joint denominator

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: NTF4
Protein: p.Pro53Ser
Coding: c.157C>T
MANE Select: NM_006179
dbSNP: rs1017274820
Type: single nucleotide variant
Location: chr19:49061841 (GRCh38)
Gene constraint: LOEUF 1.493 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 78.69 · 3 PDB

Full NTF4 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

NTF4 p.Gln174Arg Likely pathogenic ★ same condition
NTF4 p.Ala127Ser Uncertain significance ★ ⚠ same condition
NTF4 p.Ala172Thr Uncertain significance ★ ⚠ same condition
NTF4 p.Ala54Thr Uncertain significance ★ ⚠ same condition
NTF4 p.Ala71Val Uncertain significance ★ ⚠ same condition
NTF4 p.Ala73Val Uncertain significance ★ ⚠ same condition
NTF4 p.Arg107His Uncertain significance ★ ⚠ same condition
NTF4 p.Arg108Gln 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/ntf4-p-pro53ser (accessed [today's date]).

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