Is DPT p.Tyr103Phe (c.308A>T) pathogenic?

DPT p.Tyr103Phe (c.308A>T) is classified Uncertain significance in DPT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-18). AlphaMissense: likely benign (0.1339); Very rare (popmax 0.00534%, afr).

How common is DPT p.Tyr103Phe (c.308A>T) in the general population?

DPT p.Tyr103Phe (c.308A>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about DPT p.Tyr103Phe (c.308A>T)?

AlphaMissense predicts likely benign (score 0.1339) — an in-silico prediction, not a clinical call.

DPT p.Tyr103Phe

c.308A>T · VCV3842327

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1339 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1339	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -5.44	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 6.2	GERP 2.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 33 kb · p 0.84 · regional, not allelic
Overall
CADD	23.8	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 0.00534% African / African-American · 4/74,868 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,613,970 alleles · very rare

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.Tyr103Phe
Coding: c.308A>T
MANE Select: NM_001937
Type: single nucleotide variant
Location: chr1:168714344 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.21
Residue 103: a disulfide bond; the '2 x 53-55 aa tandem repeats' region; the '3 x 6 aa repeats of d-r-[eq]-w-[nqk]-[fy]' region

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

Similar variants

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
DPT p.Arg134His 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-tyr103phe (accessed [today's date]).

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