Is UCP3 p.Phe91= (c.273C>T) pathogenic?

UCP3 p.Phe91= (c.273C>T) is classified Likely benign in UCP3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-02-28). Very rare (popmax 0.00533%, afr); Associated with UCP3-related disorder.

What condition is associated with UCP3 p.Phe91= (c.273C>T)?

UCP3 p.Phe91= (c.273C>T) is associated with UCP3-related disorder (ClinVar).

How common is UCP3 p.Phe91= (c.273C>T) in the general population?

UCP3 p.Phe91= (c.273C>T) is very rare (popmax 0.00533%, afr) (gnomAD).

UCP3 p.Phe91=

c.273C>T · rs150693088 · VCV3032248

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Conditions

UCP3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.39	GERP -3, phastCons 0.002
Overall
CADD	9.973	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00533% African / African-American · 4/75,062 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00254% 41/1,614,118 alleles · very rare exomes 34/1,461,774 · genomes 7/152,344 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.008%	12,501
African / African-Americangrpmax	0.00533%	18,765
South Asian	0.00439%	22,771
European (non-Finnish)	0.00229%	43,705
Admixed American	0.00167%	60,020

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: UCP3
Protein: p.Phe91=
Coding: c.273C>T
MANE Select: NM_003356
dbSNP: rs150693088
Type: single nucleotide variant
Location: chr11:74006233 (GRCh38)
Gene constraint: LOEUF 1.2 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.65

Full UCP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

UCP3-related disorder

Similar variants

UCP3 p.Val142Ile Uncertain significance ★★ ⚠ same condition
UCP3 c.824+1G>A Benign ★★ same condition
UCP3 p.Val304Gly Uncertain significance ★ ⚠ same condition
UCP3 p.Ala130Val Uncertain significance ⚠ same condition
UCP3 p.Ala224Thr Uncertain significance ⚠ same condition
UCP3 p.Ala227Val Uncertain significance ⚠ same condition
UCP3 p.Ala231Val Uncertain significance ⚠ same condition
UCP3 p.Ala24Ser 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/ucp3-p-phe91 (accessed [today's date]).

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