Is DHX38 p.Ser232= (c.696G>A) pathogenic?

DHX38 p.Ser232= (c.696G>A) is classified Likely benign in DHX38 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-25). Very rare (popmax 0.00667%, amr); Associated with inherited retinal dystrophy.

What condition is associated with DHX38 p.Ser232= (c.696G>A)?

DHX38 p.Ser232= (c.696G>A) is associated with inherited retinal dystrophy (ClinVar).

How common is DHX38 p.Ser232= (c.696G>A) in the general population?

DHX38 p.Ser232= (c.696G>A) is very rare (popmax 0.00667%, amr) (gnomAD).

DHX38 p.Ser232=

c.696G>A · rs556379177 · VCV1121925

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Conditions

inherited retinal dystrophy

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 -11	GERP -4.7
Overall
CADD	0.406	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/59,992 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00105% 17/1,613,842 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,998
Remaining individualsnot grpmax-eligible	0.0016%	62,484
Finnishnot grpmax-eligible	0.00156%	64,014
South Asian	0.0011%	91,072
European (non-Finnish)	0.000847%	117,999

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: DHX38
Protein: p.Ser232=
Coding: c.696G>A
MANE Select: NM_014003
dbSNP: rs556379177
Type: single nucleotide variant
Location: chr16:72098724 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.82 · 5 PDB
Residue 232: the 'disordered' region

Full DHX38 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DHX38 p.Ser232Leu Uncertain significance ★★ ⚠ same residue
DHX38 p.Ser232Ala Uncertain significance ★ same residue
DHX38 c.2011-3C>A Uncertain significance ★★ same condition
DHX38 p.Ala113Val Uncertain significance ★★ ⚠ same condition
DHX38 p.Ala403Thr Uncertain significance ★★ ⚠ same condition
DHX38 p.Ala770Val Uncertain significance ★★ ⚠ same condition
DHX38 p.Arg1045Gln Uncertain significance ★★ ⚠ same condition
DHX38 p.Arg1162His 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/dhx38-p-ser232 (accessed [today's date]).

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