Is STK38 p.Asp59Val (c.176A>T) pathogenic?

STK38 p.Asp59Val (c.176A>T) is classified Uncertain significance in STK38 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely benign (0.1683); Very rare (popmax 0.00401%, afr).

How common is STK38 p.Asp59Val (c.176A>T) in the general population?

STK38 p.Asp59Val (c.176A>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about STK38 p.Asp59Val (c.176A>T)?

AlphaMissense predicts likely benign (score 0.1683) — an in-silico prediction, not a clinical call.

STK38 p.Asp59Val

c.176A>T · VCV3450711

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1683 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1683	likely benign
REVEL	0.204	benign-leaning
SaProt	LLR -9.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.99 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 40 kb · p 1.4e-06 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,894 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,613,682 alleles · very rare exomes 3/1,461,500 · genomes 1/152,182 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,965
European (non-Finnish)	8.48e-05%	1,179,782

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: STK38
Protein: p.Asp59Val
Coding: c.176A>T
MANE Select: NM_007271
Type: single nucleotide variant
Location: chr6:36525598 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 84.80 · 2 PDB

Full STK38 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

STK38 p.Ala123Thr Uncertain significance ★ ⚠ same type
STK38 p.Ala136Val Uncertain significance ★ ⚠ same type
STK38 p.Ala290Ser Uncertain significance ★ ⚠ same type
STK38 p.Ala353Pro Uncertain significance ★ ⚠ same type
STK38 p.Ala456Glu Uncertain significance ★ same type
STK38 p.Arg104Trp Uncertain significance ★ ⚠ same type
STK38 p.Arg121Cys Uncertain significance ★ ⚠ same type
STK38 p.Arg276Cys 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/stk38-p-asp59val (accessed [today's date]).

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