Is SETD7 p.Asp306Asn (c.916G>A) pathogenic?

SETD7 p.Asp306Asn (c.916G>A) is classified Uncertain significance in SETD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.1893); Very rare (popmax 0.00223%, eas).

How common is SETD7 p.Asp306Asn (c.916G>A) in the general population?

SETD7 p.Asp306Asn (c.916G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about SETD7 p.Asp306Asn (c.916G>A)?

AlphaMissense predicts likely benign (score 0.1893) — an in-silico prediction, not a clinical call.

SETD7 p.Asp306Asn

c.916G>A · rs755336121 · VCV2354425

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1893 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1893	likely benign
REVEL	0.517	indeterminate
SaProt	LLR -10.25	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.2, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 6,178 bp · p 0.24 · regional, not allelic
Overall
CADD	27.1	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 · 1/44,846 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00118% 19/1,612,692 alleles · very rare exomes 17/1,460,534 · genomes 2/152,158 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,846
Admixed American	0.00167%	59,906
European (non-Finnish)	0.00136%	73,707
South Asian	0.0011%	90,864

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: SETD7
Protein: p.Asp306Asn
Coding: c.916G>A
MANE Select: NM_030648
dbSNP: rs755336121
Type: single nucleotide variant
Location: chr4:139517889 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 94.51 · 32 PDB
Residue 306: the set domain; a β-strand

Full SETD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SETD7 p.Pro22= Benign ★★ same type
SETD7 p.Arg115Cys Uncertain significance ★ ⚠ same type
SETD7 p.Arg179Thr Uncertain significance ★ ⚠ same type
SETD7 p.Asp101His Uncertain significance ★ ⚠ same type
SETD7 p.Cys288Ser Uncertain significance ★ ⚠ same type
SETD7 p.Cys288Tyr Uncertain significance ★ ⚠ same type
SETD7 p.Cys303Ser Uncertain significance ★ ⚠ same type
SETD7 p.Gly102Arg Uncertain significance ★ ⚠ 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/setd7-p-asp306asn (accessed [today's date]).

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