Is DDHD2 p.Gln173Ter (c.517C>T) pathogenic?

DDHD2 p.Gln173Ter (c.517C>T) is classified Likely pathogenic in DDHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-05-01). Very rare (popmax 0.00017%, nfe).

How common is DDHD2 p.Gln173Ter (c.517C>T) in the general population?

DDHD2 p.Gln173Ter (c.517C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

DDHD2 p.Gln173Ter

c.517C>T · rs1424300803 · VCV444744

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 18
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.75 · evaluated, not missing
Pangolin	Δ0.34	loss · gain 0.28 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,876 alleles

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

Overall 0.000137% 2/1,457,934 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: DDHD2
Protein: p.Gln173Ter
Coding: c.517C>T
MANE Select: NM_015214
dbSNP: rs1424300803
Type: single nucleotide variant
Location: chr8:38238104 (GRCh38)
Gene constraint: LOEUF 0.758 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.70

Full DDHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PLPP5 p.Cys173Gly Uncertain significance ★ ⚠ same residue
DDHD2 c.1126-2A>G Likely pathogenic ★★ same type
DDHD2 c.1248+2T>C Likely pathogenic ★★ same type
DDHD2 p.Arg232Ter Pathogenic ★★ same type
DDHD2 p.Arg329Ter Pathogenic ★★ same type
DDHD2 p.Arg422Ter Likely pathogenic ★★ same type
DDHD2 p.Arg516Ter Pathogenic ★★ same type
DDHD2 p.Asp660His Pathogenic/Likely pathogenic ★★ 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/ddhd2-p-gln173ter (accessed [today's date]).

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