Is NT5C3B p.Phe153Ser (c.458T>C) pathogenic?

NT5C3B p.Phe153Ser (c.458T>C) is classified Uncertain significance in NT5C3B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-09). AlphaMissense: likely pathogenic (0.5798); Ultra-rare (popmax 0.014%, nfe).

How common is NT5C3B p.Phe153Ser (c.458T>C) in the general population?

NT5C3B p.Phe153Ser (c.458T>C) is ultra-rare (popmax 0.014%, nfe) (gnomAD).

What do computational predictors say about NT5C3B p.Phe153Ser (c.458T>C)?

AlphaMissense predicts likely pathogenic (score 0.5798) — an in-silico prediction, not a clinical call.

NT5C3B p.Phe153Ser

c.458T>C · rs144991098 · VCV2407951

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5798 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.014%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5798	likely pathogenic
REVEL	0.772	pathogenic-leaning
SaProt	LLR -14.89	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8	GERP 2.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 11 kb · p 0.78 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.014% European (non-Finnish) · 165/1,179,826 alleles

Filtering AF 0.0122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0116%

Overall 0.0108% 174/1,613,874 alleles · ultra-rare exomes 161/1,461,636 · genomes 13/152,238 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.014%	7,150
Remaining individualsnot grpmax-eligible	0.0112%	8,926
African / African-American	0.00267%	37,473

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: NT5C3B
Protein: p.Phe153Ser
Coding: c.458T>C
MANE Select: NM_052935
dbSNP: rs144991098
Type: single nucleotide variant
Location: chr17:41828899 (GRCh38)
Gene constraint: LOEUF 1.386 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.76 · 3 PDB
Residue 153: a β-strand

Full NT5C3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NT5C3B p.Ala109Val Uncertain significance ★ ⚠ same type
NT5C3B p.Arg260Trp Uncertain significance ★ ⚠ same type
NT5C3B p.Arg261Gln Uncertain significance ★ ⚠ same type
NT5C3B p.Arg93Gln Uncertain significance ★ ⚠ same type
NT5C3B p.Asn111Ser Uncertain significance ★ ⚠ same type
NT5C3B p.Asn149Ser Uncertain significance ★ ⚠ same type
NT5C3B p.Asp189Asn Uncertain significance ★ ⚠ same type
NT5C3B p.Asp239Asn 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/nt5c3b-p-phe153ser (accessed [today's date]).

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