Is DPT p.Ser69Thr (c.205T>A) pathogenic?

DPT p.Ser69Thr (c.205T>A) is classified Likely benign in DPT (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: ambiguous (0.3706); Rare (popmax 0.308%, nfe).

How common is DPT p.Ser69Thr (c.205T>A) in the general population?

DPT p.Ser69Thr (c.205T>A) is rare (popmax 0.308%, nfe) (gnomAD).

What do computational predictors say about DPT p.Ser69Thr (c.205T>A)?

AlphaMissense predicts ambiguous (score 0.3706) — an in-silico prediction, not a clinical call.

DPT p.Ser69Thr

c.205T>A · rs143980534 · VCV710259

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3706 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.308%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3706	ambiguous
REVEL	0.213	benign-leaning
SaProt	LLR -7.69	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.33	donor gain · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 33 kb · p 0.84 · regional, not allelic
Overall
CADD	27.2	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 0.308% European (non-Finnish) · 3,629/1,180,026 alleles

Filtering AF 0.299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.296%

Overall 0.244% 3,936/1,614,126 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.308%	325
Finnishnot grpmax-eligible	0.203%	493
Remaining individualsnot grpmax-eligible	0.168%	595
African / African-American	0.0587%	1,705
Admixed American	0.0417%	2,400
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
South Asian	0.0022%	45,539

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: DPT
Protein: p.Ser69Thr
Coding: c.205T>A
MANE Select: NM_001937
dbSNP: rs143980534
Type: single nucleotide variant
Location: chr1:168728970 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.21
Residue 69: a disulfide bond; the '2 x 53-55 aa tandem repeats' region

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

Similar variants

DPT p.Ser69Pro Uncertain significance ★ ⚠ same residue
DPT p.Ala58= Benign ★★ same type
DPT p.Phe130= Likely benign ★★ same type
DPT p.Ser83Ile Likely benign ★★ same type
DPT p.Tyr194= Benign ★★ same type
DPT p.Val201Ile Benign ★★ same type
DPT p.Arg126Gln Uncertain significance ★ ⚠ same type
DPT p.Arg134Cys 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/dpt-p-ser69thr (accessed [today's date]).

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