Is DDHD1 p.Thr296Pro (c.886A>C) pathogenic?

DDHD1 p.Thr296Pro (c.886A>C) is classified Uncertain significance in DDHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-18). AlphaMissense: likely pathogenic (0.7631); Very rare (popmax 0.00893%, eas); Associated with Inborn genetic diseases.

What condition is associated with DDHD1 p.Thr296Pro (c.886A>C)?

DDHD1 p.Thr296Pro (c.886A>C) is associated with Inborn genetic diseases (ClinVar).

How common is DDHD1 p.Thr296Pro (c.886A>C) in the general population?

DDHD1 p.Thr296Pro (c.886A>C) is very rare (popmax 0.00893%, eas) (gnomAD).

What do computational predictors say about DDHD1 p.Thr296Pro (c.886A>C)?

AlphaMissense predicts likely pathogenic (score 0.7631) — an in-silico prediction, not a clinical call.

DDHD1 p.Thr296Pro

c.886A>C · rs765039754 · VCV2537877

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7631 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00893%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7631	likely pathogenic
REVEL	0.255	benign-leaning
SaProt	LLR -13.09	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 106 kb · p 7.8e-05 · regional, not allelic
Overall
CADD	28.1	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 0.00893% East Asian · 4/44,778 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000372% 6/1,612,758 alleles · very rare exomes 6/1,460,422 · genomes 0/152,336 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00893%	11,194
Remaining individualsnot grpmax-eligible	0.0032%	31,226

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.Thr296Pro
Coding: c.886A>C
MANE Select: NM_001160148
dbSNP: rs765039754
Type: single nucleotide variant
Location: chr14:53103809 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DDHD1 p.Ala94Pro Uncertain significance ★★ ⚠ same condition
DDHD1 p.Arg204Trp 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
DDHD1 p.Arg732His Uncertain significance ★★ ⚠ same condition
DDHD1 p.Asn279Ser Uncertain significance ★★ ⚠ same condition
DDHD1 p.Asn688Ser 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-thr296pro (accessed [today's date]).

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