Is DPH6 p.Thr86Ala (c.256A>G) pathogenic?

DPH6 p.Thr86Ala (c.256A>G) is classified Uncertain significance in DPH6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-15). AlphaMissense: likely benign (0.0762); Very rare (popmax 0.00167%, amr).

How common is DPH6 p.Thr86Ala (c.256A>G) in the general population?

DPH6 p.Thr86Ala (c.256A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DPH6 p.Thr86Ala (c.256A>G)?

AlphaMissense predicts likely benign (score 0.0762) — an in-silico prediction, not a clinical call.

DPH6 p.Thr86Ala

c.256A>G · VCV4014570

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0762 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0762	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -9.41	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 1.2	GERP -0.33, phastCons 0.92
Regional constraint	o/e 1.02	unconstrained · MANE · 174 kb · p 0.78 · regional, not allelic
Overall
CADD	18.96	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 0.00167% Admixed American · 1/59,956 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000497% 8/1,609,034 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,956
Remaining individualsnot grpmax-eligible	0.00161%	62,244
European (non-Finnish)	0.00051%	196,038

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: DPH6
Protein: p.Thr86Ala
Coding: c.256A>G
MANE Select: NM_080650
Type: single nucleotide variant
Location: chr15:35538330 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.85

Full DPH6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPH6 p.Gly41Glu Benign ★★ same type
DPH6 p.Ala5Ser Uncertain significance ★ ⚠ same type
DPH6 p.Arg123His Uncertain significance ★ ⚠ same type
DPH6 p.Arg241His Uncertain significance ★ ⚠ same type
DPH6 p.Arg2Trp Uncertain significance ★ ⚠ same type
DPH6 p.Asp173Ala Uncertain significance ★ ⚠ same type
DPH6 p.Asp173His Uncertain significance ★ ⚠ same type
DPH6 p.Asp46Asn 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/dph6-p-thr86ala (accessed [today's date]).

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