DHX37 p.Ala1065=

Q: Is DHX37 p.Ala1065= (c.3195C>T) pathogenic?

DHX37 p.Ala1065= (c.3195C>T) is classified Benign in DHX37 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). Common (popmax 58.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies.

Q: What condition is associated with DHX37 p.Ala1065= (c.3195C>T)?

DHX37 p.Ala1065= (c.3195C>T) is associated with neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies, 46,XY sex reversal 11 (ClinVar).

Q: How common is DHX37 p.Ala1065= (c.3195C>T) in the general population?

DHX37 p.Ala1065= (c.3195C>T) is common (popmax 58.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3195C>T · rs4078216 · VCV1255484

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 58.1%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies

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 1.2	GERP -1.7, phastCons 1
Overall
CADD	7.461	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 58.1% East Asian · 26,066/44,856 alleles

Filtering AF 57.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 57.3%

Overall 24.6% 396,639/1,613,888 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	58.1%	2
Admixed American	30.4%	3
Finnishnot grpmax-eligible	29.2%	3
South Asian	28.8%	3
Remaining individualsnot grpmax-eligible	24.6%	4
European (non-Finnish)	23.6%	4
Ashkenazi Jewishnot grpmax-eligible	22.7%	4
Middle Eastern	20.9%	5
Amishnot grpmax-eligible	12.9%	8
African / African-American	7.89%	13

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: DHX37
Protein: p.Ala1065=
Coding: c.3195C>T
MANE Select: NM_032656
dbSNP: rs4078216
Type: single nucleotide variant
Location: chr12:124950170 (GRCh38)
Gene constraint: LOEUF 0.518 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 76.27 · 1 PDB
Residue 1065: an α-helix

Full DHX37 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: 46,XY sex reversal 11

Similar variants

DHX37 p.Arg308Gln Pathogenic ★★ same condition
DHX37 p.Arg674Trp Likely pathogenic ★★ same condition
DHX37 p.Ala469Ser Uncertain significance ★★ ⚠ same condition
DHX37 p.Arg1029Pro Uncertain significance ★★ ⚠ same condition
DHX37 p.Arg1101His Uncertain significance ★★ ⚠ same condition
DHX37 p.Arg151Trp Uncertain significance ★★ ⚠ same condition
DHX37 p.Arg458Trp Uncertain significance ★★ ⚠ same condition
DHX37 p.Arg833Gln 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/dhx37-p-ala1065 (accessed [today's date]).

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