Is DPH6 p.Ala5Ser (c.13G>T) pathogenic?

DPH6 p.Ala5Ser (c.13G>T) is classified Uncertain significance in DPH6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-01). AlphaMissense: ambiguous (0.3738); Very rare (popmax 0.00442%, afr).

How common is DPH6 p.Ala5Ser (c.13G>T) in the general population?

DPH6 p.Ala5Ser (c.13G>T) is very rare (popmax 0.00442%, afr) (gnomAD).

What do computational predictors say about DPH6 p.Ala5Ser (c.13G>T)?

AlphaMissense predicts ambiguous (score 0.3738) — an in-silico prediction, not a clinical call.

DPH6 p.Ala5Ser

c.13G>T · VCV3273596

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3738 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00442%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3738	ambiguous
REVEL	0.236	benign-leaning
SaProt	LLR -8.87	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 174 kb · p 0.78 · regional, not allelic
Overall
CADD	28.3	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 0.00442% African / African-American · 3/67,834 alleles

Filtering AF 0.00117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000626%

Overall 0.000925% 13/1,405,746 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00442%	22,611
East Asian	0.00304%	32,852
European (non-Finnish)	0.000844%	118,420

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.Ala5Ser
Coding: c.13G>T
MANE Select: NM_080650
Type: single nucleotide variant
Location: chr15:35546129 (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.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
DPH6 p.Cys199Phe 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-ala5ser (accessed [today's date]).

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