Is DDHD1 p.Lys836= (c.2508A>G) pathogenic?

DDHD1 p.Lys836= (c.2508A>G) is classified Likely benign in DDHD1 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-05-01). Ultra-rare (popmax 0.0526%, nfe).

How common is DDHD1 p.Lys836= (c.2508A>G) in the general population?

DDHD1 p.Lys836= (c.2508A>G) is ultra-rare (popmax 0.0526%, nfe) (gnomAD).

DDHD1 p.Lys836=

c.2508A>G · rs375235517 · VCV2644242

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0526%, nfe)

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 7.9	GERP 2, phastCons 1
Overall
CADD	11.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0526% European (non-Finnish) · 616/1,170,922 alleles

Filtering AF 0.0491% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0477%

Overall 0.0435% 695/1,597,540 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.071%	1,408
European (non-Finnish)grpmax	0.0526%	1,901
Admixed American	0.0362%	2,764
African / African-American	0.0147%	6,786
Finnishnot grpmax-eligible	0.00474%	21,091

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys836=
Coding: c.2508A>G
MANE Select: NM_001160148
dbSNP: rs375235517
Type: single nucleotide variant
Location: chr14:53051857 (GRCh38)
Gene constraint: LOEUF 0.642 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 67.11
Residue 836: the ddhd domain

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

Similar variants

DDHD1 p.Ala193Val Uncertain significance ★★ ⚠ same type
DDHD1 p.Ala94Pro Uncertain significance ★★ ⚠ same type
DDHD1 p.Arg204Trp Uncertain significance ★★ ⚠ same type
DDHD1 p.Arg288His Uncertain significance ★★ ⚠ same type
DDHD1 p.Arg554Gln Uncertain significance ★★ ⚠ same type
DDHD1 p.Arg570Gln Uncertain significance ★★ ⚠ same type
DDHD1 p.Arg588Gln Uncertain significance ★★ ⚠ same type
DDHD1 p.Arg596Gln 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/ddhd1-p-lys836 (accessed [today's date]).

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