Is UTP14C p.Ile170Val (c.508A>G) pathogenic?

UTP14C p.Ile170Val (c.508A>G) is classified Conflicting classifications of pathogenicity in UTP14C (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-10-01). AlphaMissense: likely benign (0.0726); Rare (popmax 0.751%, nfe); Associated with ALG11-congenital disorder of glycosylation.

What condition is associated with UTP14C p.Ile170Val (c.508A>G)?

UTP14C p.Ile170Val (c.508A>G) is associated with ALG11-congenital disorder of glycosylation (ClinVar).

How common is UTP14C p.Ile170Val (c.508A>G) in the general population?

UTP14C p.Ile170Val (c.508A>G) is rare (popmax 0.751%, nfe) (gnomAD).

How is ALG11-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about UTP14C p.Ile170Val (c.508A>G)?

AlphaMissense predicts likely benign (score 0.0726) — an in-silico prediction, not a clinical call.

UTP14C p.Ile170Val

c.508A>G · rs73184339 · VCV235513

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0726 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.751%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG11-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0726	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -4.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.4	GERP -0.72, phastCons 0.088
Regional constraint	o/e 0.92	unconstrained · MANE · 2,297 bp · p 0.015 · regional, not allelic
Overall
CADD	7.925	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 0.751% European (non-Finnish) · 8,858/1,180,036 alleles

Filtering AF 0.738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.732%

Overall 0.596% 9,624/1,614,194 alleles · rare exomes 9,000/1,461,892 · genomes 624/152,302 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.751%	133
Remaining individualsnot grpmax-eligible	0.626%	160
Admixed American	0.283%	353
African / African-American	0.135%	743
Finnishnot grpmax-eligible	0.0796%	1,256
South Asian	0.0549%	1,821
Middle Eastern	0.033%	3,031
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602

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: UTP14C
Protein: p.Ile170Val
Coding: c.508A>G
MANE Select: NM_021645
dbSNP: rs73184339
Type: single nucleotide variant
Location: chr13:52029312 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.59

Full UTP14C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG11-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG11-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG11 p.Met395Thr Likely pathogenic ★★ same condition
ALG11 p.Arg346Cys Uncertain significance ★★ ⚠ same condition
UTP14C p.Arg58Trp Uncertain significance ★★ ⚠ same condition
UTP14C p.Val157Gly Uncertain significance ★★ ⚠ same condition
ALG11 c.*468G>T Benign ★★ same condition
ALG11 c.*148A>T Uncertain significance ★ same condition
ALG11 c.*490C>T Uncertain significance ★ same condition
ALG11 c.*491G>A 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/utp14c-p-ile170val (accessed [today's date]).

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