Is SETD5 p.Asp80Asn (c.238G>A) pathogenic?

SETD5 p.Asp80Asn (c.238G>A) is classified Uncertain significance in SETD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-20). AlphaMissense: ambiguous (0.3948); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with SETD5 p.Asp80Asn (c.238G>A)?

SETD5 p.Asp80Asn (c.238G>A) is associated with Inborn genetic diseases (ClinVar).

How common is SETD5 p.Asp80Asn (c.238G>A) in the general population?

SETD5 p.Asp80Asn (c.238G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about SETD5 p.Asp80Asn (c.238G>A)?

AlphaMissense predicts ambiguous (score 0.3948) — an in-silico prediction, not a clinical call.

SETD5 p.Asp80Asn

c.238G>A · VCV3317746

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3948 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3948	ambiguous
REVEL	0.353	indeterminate
SaProt	LLR -6.51	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 12 kb · p 2.7e-05 · regional, not allelic
Overall
CADD	33.0	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 0.00223% East Asian · 1/44,880 alleles

Overall 6.2e-05% 1/1,613,964 alleles · very rare exomes 1/1,461,698 · genomes 0/152,266 · 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: SETD5
Protein: p.Asp80Asn
Coding: c.238G>A
MANE Select: NM_001080517
Type: single nucleotide variant
Location: chr3:9434394 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 47.10

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SETD5 c.2347-7A>G Pathogenic ★★ same condition
SETD5 p.Arg1001Ter Pathogenic ★★ same condition
SETD5 p.Arg308Ter Pathogenic/Likely pathogenic ★★ same condition
SETD5 p.Arg361Ter Pathogenic ★★ same condition
SETD5 p.Gln1101Ter Pathogenic ★★ same condition
SETD5 p.Ser668Ter Pathogenic/Likely pathogenic ★★ same condition
SETD5 p.Ala1112Ser Uncertain significance ★★ ⚠ same condition
SETD5 p.Ala4Ser 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/setd5-p-asp80asn (accessed [today's date]).

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