Is SETD5 p.Ile5Val (c.13A>G) pathogenic?

SETD5 p.Ile5Val (c.13A>G) is classified Conflicting classifications of pathogenicity in SETD5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-19). AlphaMissense: likely benign (0.121); Very rare (popmax 0.00892%, eas); Associated with Inborn genetic diseases.

What condition is associated with SETD5 p.Ile5Val (c.13A>G)?

SETD5 p.Ile5Val (c.13A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SETD5 p.Ile5Val (c.13A>G) in the general population?

SETD5 p.Ile5Val (c.13A>G) is very rare (popmax 0.00892%, eas) (gnomAD).

What do computational predictors say about SETD5 p.Ile5Val (c.13A>G)?

AlphaMissense predicts likely benign (score 0.121) — an in-silico prediction, not a clinical call.

SETD5 p.Ile5Val

c.13A>G · rs567415895 · VCV1367201

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.121 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.121	likely benign
REVEL	0.243	benign-leaning
SaProt	LLR -4.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -2.9, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 12 kb · p 2.7e-05 · regional, not allelic
Overall
CADD	17.79	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 0.00892% East Asian · 4/44,852 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00198% 32/1,613,136 alleles · very rare exomes 28/1,460,874 · genomes 4/152,262 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,213
Finnishnot grpmax-eligible	0.00625%	15,994
Admixed American	0.00334%	29,980
South Asian	0.0033%	30,309
Remaining individualsnot grpmax-eligible	0.0032%	31,217
African / African-American	0.00267%	37,507
European (non-Finnish)	0.00127%	78,629

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.Ile5Val
Coding: c.13A>G
MANE Select: NM_001080517
dbSNP: rs567415895
Type: single nucleotide variant
Location: chr3:9428951 (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 p.Ile5Asn Likely benign ★ ⚠ same residue
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

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-ile5val (accessed [today's date]).

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