Is DDHD1 p.Phe316= (c.948T>C) pathogenic?

DDHD1 p.Phe316= (c.948T>C) is classified Likely benign in DDHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-06). Very rare (popmax 6.84e-05%); Associated with hereditary spastic paraplegia 28.

What condition is associated with DDHD1 p.Phe316= (c.948T>C)?

DDHD1 p.Phe316= (c.948T>C) is associated with hereditary spastic paraplegia 28 (ClinVar).

How common is DDHD1 p.Phe316= (c.948T>C) in the general population?

DDHD1 p.Phe316= (c.948T>C) is very rare (popmax 6.84e-05%) (gnomAD).

How is Autosomal recessive spastic paraplegia type 28 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DDHD1 p.Phe316=

c.948T>C · VCV3672330

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Conditions

hereditary spastic paraplegia 28

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 0.46, phastCons 1
Overall
CADD	10.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,348 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: DDHD1
Protein: p.Phe316=
Coding: c.948T>C
MANE Select: NM_001160148
Type: single nucleotide variant
Location: chr14:53103747 (GRCh38)
Gene constraint: LOEUF 0.642 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 67.11

Full DDHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 28 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive spastic paraplegia type 28 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood, Infancy

Similar variants

DDHD1 p.Ala193Val Uncertain significance ★★ ⚠ same condition
DDHD1 p.Ala94Pro Uncertain significance ★★ ⚠ same condition
DDHD1 p.Arg204Trp Uncertain significance ★★ ⚠ same condition
DDHD1 p.Arg288His Uncertain significance ★★ ⚠ same condition
DDHD1 p.Arg554Gln Uncertain significance ★★ ⚠ same condition
DDHD1 p.Arg570Gln Uncertain significance ★★ ⚠ same condition
DDHD1 p.Arg588Gln Uncertain significance ★★ ⚠ same condition
DDHD1 p.Arg596Gln 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/ddhd1-p-phe316 (accessed [today's date]).

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