Is SETD5 p.Val360Leu (c.1078G>T) pathogenic?

SETD5 p.Val360Leu (c.1078G>T) is classified Uncertain significance in SETD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-17). AlphaMissense: likely pathogenic (0.979); No allele count reported in gnomAD v4.1 (AN 1,549,988); Associated with intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency.

How common is SETD5 p.Val360Leu (c.1078G>T) in the general population?

SETD5 p.Val360Leu (c.1078G>T) is no allele count reported in gnomAD v4.1 (AN 1,549,988) (gnomAD).

What do computational predictors say about SETD5 p.Val360Leu (c.1078G>T)?

AlphaMissense predicts likely pathogenic (score 0.979) — an in-silico prediction, not a clinical call.

SETD5 p.Val360Leu

Q: What condition is associated with SETD5 p.Val360Leu (c.1078G>T)?

SETD5 p.Val360Leu (c.1078G>T) is associated with intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency (ClinVar).

c.1078G>T · VCV4291116

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.979 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,549,988)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency

Computational evidence

Protein change
AlphaMissense	0.979	likely pathogenic · top 10% in SETD5
REVEL	0.726	pathogenic-leaning
SaProt	LLR -9.29	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	Δ0.47	acceptor gain · deltas
Pangolin	Δ0.44	loss · gain 0.18 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.41	unconstrained · MANE · 2,937 bp · p 5e-10 · regional, not allelic
Overall
CADD	35.0	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

No allele count reported in gnomAD v4.1 (AN 1,549,988). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SETD5
Protein: p.Val360Leu
Coding: c.1078G>T
MANE Select: NM_001080517
Type: single nucleotide variant
Location: chr3:9443308 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 47.10
Residue 360: the set domain

Full SETD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SETD5 c.1441-1G>A Pathogenic ★★ same condition
SETD5 c.1525-1G>C Pathogenic/Likely pathogenic ★★ same condition
SETD5 c.2347-7A>G Pathogenic ★★ same condition
SETD5 c.3631+1G>A Pathogenic ★★ same condition
SETD5 c.960-5C>G Pathogenic/Likely pathogenic ★★ same condition
SETD5 p.Arg1001Ter Pathogenic ★★ same condition
SETD5 p.Arg1072Ter Pathogenic/Likely pathogenic ★★ same condition
SETD5 p.Arg1121Ter Pathogenic ★★ 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/setd5-p-val360leu (accessed [today's date]).

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