Is UCK2 p.Ser116Phe (c.347C>T) pathogenic?

UCK2 p.Ser116Phe (c.347C>T) is classified Uncertain significance in UCK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: ambiguous (0.3526); Very rare (popmax 0.00167%, amr).

How common is UCK2 p.Ser116Phe (c.347C>T) in the general population?

UCK2 p.Ser116Phe (c.347C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about UCK2 p.Ser116Phe (c.347C>T)?

AlphaMissense predicts ambiguous (score 0.3526) — an in-silico prediction, not a clinical call.

UCK2 p.Ser116Phe

c.347C>T · VCV4195464

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3526 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3526	ambiguous
REVEL	0.259	benign-leaning
SaProt	LLR -14.32	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 68 kb · p 8.5e-06 · regional, not allelic
Overall
CADD	27.4	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 0.00167% Admixed American · 1/60,032 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000743% 12/1,614,190 alleles · very rare exomes 12/1,461,818 · genomes 0/152,372 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,032
European (non-Finnish)	0.000932%	107,272

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: UCK2
Protein: p.Ser116Phe
Coding: c.347C>T
MANE Select: NM_012474
Type: single nucleotide variant
Location: chr1:165891313 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.52 · 11 PDB
Residue 116: a turn

Full UCK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UCK2 p.Ala253Thr Uncertain significance ★ ⚠ same type
UCK2 p.Asn243Asp Uncertain significance ★ ⚠ same type
UCK2 p.Gln7His Uncertain significance ★ ⚠ same type
UCK2 p.Glu173Lys Uncertain significance ★ same type
UCK2 p.Gly175Arg Uncertain significance ★ ⚠ same type
UCK2 p.Ile109Met Uncertain significance ★ same type
UCK2 p.Ile218Val Uncertain significance ★ ⚠ same type
UCK2 p.Phe81Leu 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/uck2-p-ser116phe (accessed [today's date]).

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