Is UFSP2 p.Val403Phe (c.1207G>T) pathogenic?

UFSP2 p.Val403Phe (c.1207G>T) is classified Uncertain significance in UFSP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-25). AlphaMissense: ambiguous (0.5088); Very rare (popmax 0.005%, nfe).

How common is UFSP2 p.Val403Phe (c.1207G>T) in the general population?

UFSP2 p.Val403Phe (c.1207G>T) is very rare (popmax 0.005%, nfe) (gnomAD).

What do computational predictors say about UFSP2 p.Val403Phe (c.1207G>T)?

AlphaMissense predicts ambiguous (score 0.5088) — an in-silico prediction, not a clinical call.

UFSP2 p.Val403Phe

c.1207G>T · VCV4969139

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5088 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5088	ambiguous
REVEL	0.876	moderately pathogenic-leaning
SaProt	LLR -14.17	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 25 kb · p 0.022 · regional, not allelic
Overall
CADD	29.0	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 0.005% European (non-Finnish) · 59/1,179,086 alleles

Filtering AF 0.00394% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00361%

Overall 0.00366% 59/1,610,434 alleles · very rare exomes 59/1,458,206 · genomes 0/152,228 · 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: UFSP2
Protein: p.Val403Phe
Coding: c.1207G>T
MANE Select: NM_018359
Type: single nucleotide variant
Location: chr4:185403610 (GRCh38)
Gene constraint: LOEUF 0.935 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.21

Full UFSP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UFSP2 p.Asp426Ala Pathogenic ★★ same type
UFSP2 p.His428Arg Likely pathogenic ★★ same type
UFSP2 p.Gly286Ala Uncertain significance ★★ ⚠ same type
UFSP2 p.Gly346Arg Uncertain significance ★★ ⚠ same type
UFSP2 p.Ala432= Benign ★★ same type
UFSP2 p.Cys311Ser Benign/Likely benign ★★ ⚠ same type
UFSP2 p.Glu321= Benign/Likely benign ★★ same type
UFSP2 p.Asp426Gly Likely pathogenic ★ 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/ufsp2-p-val403phe (accessed [today's date]).

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