Is DPH6 p.Pro236Ser (c.706C>T) pathogenic?

DPH6 p.Pro236Ser (c.706C>T) is classified Uncertain significance in DPH6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.3043); Ultra-rare (popmax 0.0941%, sas).

How common is DPH6 p.Pro236Ser (c.706C>T) in the general population?

DPH6 p.Pro236Ser (c.706C>T) is ultra-rare (popmax 0.0941%, sas) (gnomAD).

What do computational predictors say about DPH6 p.Pro236Ser (c.706C>T)?

AlphaMissense predicts likely benign (score 0.3043) — an in-silico prediction, not a clinical call.

DPH6 p.Pro236Ser

c.706C>T · VCV4244429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3043 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0941%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3043	likely benign
REVEL	0.418	indeterminate
SaProt	LLR -9.07	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 174 kb · p 0.78 · regional, not allelic
Overall
CADD	26.8	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 0.0941% South Asian · 85/90,298 alleles

Filtering AF 0.0779% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0719%

Overall 0.00547% 88/1,608,628 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0941%	1,062
Remaining individualsnot grpmax-eligible	0.00321%	31,127
European (non-Finnish)	8.49e-05%	1,177,468

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.Pro236Ser
Coding: c.706C>T
MANE Select: NM_080650
Type: single nucleotide variant
Location: chr15:35373565 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.85
Residue 236: a UniProt-annotated variant site (in)

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-pro236ser (accessed [today's date]).

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