Is DPY19L4 p.Ser709Thr (c.2125T>A) pathogenic?

DPY19L4 p.Ser709Thr (c.2125T>A) is classified Uncertain significance in DPY19L4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-11). AlphaMissense: likely benign (0.1293); Very rare (popmax 0.00686%, amr).

How common is DPY19L4 p.Ser709Thr (c.2125T>A) in the general population?

DPY19L4 p.Ser709Thr (c.2125T>A) is very rare (popmax 0.00686%, amr) (gnomAD).

What do computational predictors say about DPY19L4 p.Ser709Thr (c.2125T>A)?

AlphaMissense predicts likely benign (score 0.1293) — an in-silico prediction, not a clinical call.

DPY19L4 p.Ser709Thr

c.2125T>A · VCV4014724

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1293 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00686%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1293	likely benign
REVEL	0.269	benign-leaning
SaProt	LLR -4.67	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 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 70 kb · p 0.22 · regional, not allelic
Overall
CADD	22.7	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 0.00686% Admixed American · 4/58,308 alleles

Filtering AF 0.0023% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00138%

Overall 0.000373% 6/1,607,108 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00686%	14,577
Remaining individualsnot grpmax-eligible	0.00161%	62,240
European (non-Finnish)	8.49e-05%	1,178,150

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: DPY19L4
Protein: p.Ser709Thr
Coding: c.2125T>A
MANE Select: NM_181787
Type: single nucleotide variant
Location: chr8:94789863 (GRCh38)
Gene constraint: LOEUF 1.198 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.47

Full DPY19L4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPY19L4 p.Ala230Val Uncertain significance ★ ⚠ same type
DPY19L4 p.Ala579Val Uncertain significance ★ ⚠ same type
DPY19L4 p.Ala582Val Uncertain significance ★ ⚠ same type
DPY19L4 p.Arg463Gly Uncertain significance ★ ⚠ same type
DPY19L4 p.Arg516Gln Uncertain significance ★ ⚠ same type
DPY19L4 p.Arg573Gly Uncertain significance ★ ⚠ same type
DPY19L4 p.Arg613Lys Uncertain significance ★ ⚠ same type
DPY19L4 p.Arg76Trp 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/dpy19l4-p-ser709thr (accessed [today's date]).

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