Is DPY19L2 p.Ser646= (c.1938C>T) pathogenic?

DPY19L2 p.Ser646= (c.1938C>T) is classified Likely benign in DPY19L2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-11-25). Rare (popmax 0.474%, afr).

How common is DPY19L2 p.Ser646= (c.1938C>T) in the general population?

DPY19L2 p.Ser646= (c.1938C>T) is rare (popmax 0.474%, afr) (gnomAD).

DPY19L2 p.Ser646=

c.1938C>T · VCV4387722

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.474%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.53	GERP -7.8
Overall
CADD	1.899	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.474% African / African-American · 320/67,514 alleles

Filtering AF 0.431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.414%

Overall 0.139% 2,132/1,539,240 alleles · rare exomes 1,063/1,407,958 · genomes 1,069/131,282 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.486%	206
Amishnot grpmax-eligible	0.478%	209
African / African-Americangrpmax	0.474%	211
Admixed American	0.447%	224
East Asian	0.169%	592
Remaining individualsnot grpmax-eligible	0.164%	608
Ashkenazi Jewishnot grpmax-eligible	0.128%	781
Middle Eastern	0.119%	840
South Asian	0.0929%	1,077
European (non-Finnish)	0.0877%	1,141

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DPY19L2
Protein: p.Ser646=
Coding: c.1938C>T
MANE Select: NM_173812
Type: single nucleotide variant
Location: chr12:63570820 (GRCh38)
Gene constraint: LOEUF 0.732 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.61
Residue 646: a UniProt-annotated variant site (in spgf9)

Full DPY19L2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPY19L2 p.Arg23Cys Uncertain significance ★★ ⚠ same type
DPY19L2 p.Arg10Trp Likely benign ★★ same type
DPY19L2 p.Glu98Ter Benign ★★ same type
DPY19L2 p.Arg290His Pathogenic ★ same type
DPY19L2 p.Gly273Arg Likely pathogenic ★ same type
DPY19L2 p.Lys680Ter Pathogenic ★ same type
DPY19L2 c.804-3C>A Uncertain significance ★ same type
DPY19L2 p.Ala432Thr 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/dpy19l2-p-ser646 (accessed [today's date]).

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