Is DPY19L4 p.Ala579Val (c.1736C>T) pathogenic?

DPY19L4 p.Ala579Val (c.1736C>T) is classified Uncertain significance in DPY19L4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely benign (0.2572); Very rare (popmax 0.00133%, afr).

How common is DPY19L4 p.Ala579Val (c.1736C>T) in the general population?

DPY19L4 p.Ala579Val (c.1736C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DPY19L4 p.Ala579Val (c.1736C>T)?

AlphaMissense predicts likely benign (score 0.2572) — an in-silico prediction, not a clinical call.

DPY19L4 p.Ala579Val

c.1736C>T · rs1336863505 · VCV3085629

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2572 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2572	likely benign
REVEL	0.386	indeterminate
SaProt	LLR -12.68	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 70 kb · p 0.22 · regional, not allelic
Overall
CADD	28.2	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 0.00133% African / African-American · 1/74,920 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,840 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,920
European (non-Finnish)	0.000169%	589,991

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.Ala579Val
Coding: c.1736C>T
MANE Select: NM_181787
dbSNP: rs1336863505
Type: single nucleotide variant
Location: chr8:94783690 (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.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
DPY19L4 p.Asn375Ile 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-ala579val (accessed [today's date]).

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