Is P4HTM p.Val317fs (c.949del) pathogenic?

P4HTM p.Val317fs (c.949del) is classified Uncertain significance in P4HTM (ClinVar, Single submitter, 2 submitters; last evaluated 2019-11-07). No gnomAD frequency available for this variant; Associated with hypotonia, hypoventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities.

How common is P4HTM p.Val317fs (c.949del) in the general population?

P4HTM p.Val317fs (c.949del) is no gnomAD frequency available for this variant (gnomAD).

P4HTM p.Val317fs

Q: What condition is associated with P4HTM p.Val317fs (c.949del)?

P4HTM p.Val317fs (c.949del) is associated with hypotonia, hypoventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities (ClinVar).

c.949del · rs1576608329 · VCV635798

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hypotonia, hypoventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.6	GERP -4.8

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: P4HTM
Protein: p.Val317fs
Coding: c.949del
MANE Select: NM_177939
dbSNP: rs1576608329
Type: Deletion
Location: chr3:49004922 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.94 · 1 PDB
Residue 317: a β-strand; the fe2og dioxygenase domain

Full P4HTM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypotonia, hypoventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

P4HTM p.Trp220Ter Pathogenic ★★ same condition
P4HTM p.Ser184Thr Uncertain significance ★★ ⚠ same condition
P4HTM c.1165_1166del Likely pathogenic ★ same condition
P4HTM c.436+1G>T Likely pathogenic ★ same condition
P4HTM p.Arg358His Pathogenic ★ same condition
P4HTM p.Glu312Lys Likely pathogenic ★ ⚠ same condition
P4HTM p.Thr361Ile Likely pathogenic ★ same condition
P4HTM c.1074-11dup Uncertain significance ★ same condition

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/p4htm-p-val317fs (accessed [today's date]).

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