Is DPY19L4 p.Phe310Cys (c.929T>G) pathogenic?

DPY19L4 p.Phe310Cys (c.929T>G) is classified Uncertain significance in DPY19L4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). AlphaMissense: ambiguous (0.4881); Ultra-rare (popmax 0.0161%, afr).

How common is DPY19L4 p.Phe310Cys (c.929T>G) in the general population?

DPY19L4 p.Phe310Cys (c.929T>G) is ultra-rare (popmax 0.0161%, afr) (gnomAD).

What do computational predictors say about DPY19L4 p.Phe310Cys (c.929T>G)?

AlphaMissense predicts ambiguous (score 0.4881) — an in-silico prediction, not a clinical call.

DPY19L4 p.Phe310Cys

c.929T>G · VCV3505080

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4881 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0161%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4881	ambiguous
REVEL	0.788	moderately pathogenic-leaning
SaProt	LLR -11.10	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 70 kb · p 0.22 · regional, not allelic
Overall
CADD	27.9	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 0.0161% African / African-American · 12/74,678 alleles

Filtering AF 0.00924% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00724%

Overall 0.000745% 12/1,609,722 alleles · ultra-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: DPY19L4
Protein: p.Phe310Cys
Coding: c.929T>G
MANE Select: NM_181787
Type: single nucleotide variant
Location: chr8:94765241 (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-phe310cys (accessed [today's date]).

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