Is DPT p.Glu121Lys (c.361G>A) pathogenic?

DPT p.Glu121Lys (c.361G>A) is classified Benign in DPT (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: ambiguous (0.4921); Low-frequency (popmax 1.2%, eas).

How common is DPT p.Glu121Lys (c.361G>A) in the general population?

DPT p.Glu121Lys (c.361G>A) is low-frequency (popmax 1.2%, eas) (gnomAD).

What do computational predictors say about DPT p.Glu121Lys (c.361G>A)?

AlphaMissense predicts ambiguous (score 0.4921) — an in-silico prediction, not a clinical call.

DPT p.Glu121Lys

c.361G>A · rs143369045 · VCV739601

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4921 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.2%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4921	ambiguous
REVEL	0.163	moderately benign-leaning
SaProt	LLR -3.51	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 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 33 kb · p 0.84 · regional, not allelic
Overall
CADD	23.9	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 1.2% East Asian · 540/44,868 alleles

Filtering AF 1.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.09%

Overall 0.0507% 819/1,614,074 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.2%	83
South Asian	0.0846%	1,183
Remaining individualsnot grpmax-eligible	0.0608%	1,645
African / African-American	0.036%	2,779
Middle Eastern	0.033%	3,031
Admixed American	0.0267%	3,751
European (non-Finnish)	0.01%	10,000
Finnishnot grpmax-eligible	0.00156%	64,000

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.Glu121Lys
Coding: c.361G>A
MANE Select: NM_001937
dbSNP: rs143369045
Type: single nucleotide variant
Location: chr1:168714291 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.21
Residue 121: 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-glu121lys (accessed [today's date]).

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