Is DPYSL4 p.Phe394Val (c.1180T>G) pathogenic?

DPYSL4 p.Phe394Val (c.1180T>G) is classified Uncertain significance in DPYSL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-11). AlphaMissense: likely benign (0.067); Very rare (popmax 0.00333%, amr).

How common is DPYSL4 p.Phe394Val (c.1180T>G) in the general population?

DPYSL4 p.Phe394Val (c.1180T>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about DPYSL4 p.Phe394Val (c.1180T>G)?

AlphaMissense predicts likely benign (score 0.067) — an in-silico prediction, not a clinical call.

DPYSL4 p.Phe394Val

c.1180T>G · rs774296840 · VCV2405853

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.067 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.067	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -5.43	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 -0.74	GERP -5
Regional constraint	o/e 0.89	unconstrained · MANE · 18 kb · p 0.0025 · regional, not allelic
Overall
CADD	12.83	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 0.00333% Admixed American · 2/60,024 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,461,042 alleles · very 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: DPYSL4
Protein: p.Phe394Val
Coding: c.1180T>G
MANE Select: NM_006426
dbSNP: rs774296840
Type: single nucleotide variant
Location: chr10:132202015 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.45 · 1 PDB

Full DPYSL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPYSL4 p.Ala127Gly Uncertain significance ★ ⚠ same type
DPYSL4 p.Ala130Glu Uncertain significance ★ ⚠ same type
DPYSL4 p.Ala300Thr Uncertain significance ★ ⚠ same type
DPYSL4 p.Ala349Val Uncertain significance ★ ⚠ same type
DPYSL4 p.Ala382Thr Uncertain significance ★ ⚠ same type
DPYSL4 p.Ala442Val Uncertain significance ★ ⚠ same type
DPYSL4 p.Ala489Val Uncertain significance ★ ⚠ same type
DPYSL4 p.Ala520Thr 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/dpysl4-p-phe394val (accessed [today's date]).

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