Is DMRT2 p.Leu117= (c.351G>A) pathogenic?

DMRT2 p.Leu117= (c.351G>A) is classified Likely benign in DMRT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-24). Very rare (popmax 0.000458%, nfe).

How common is DMRT2 p.Leu117= (c.351G>A) in the general population?

DMRT2 p.Leu117= (c.351G>A) is very rare (popmax 0.000458%, nfe) (gnomAD).

DMRT2 p.Leu117=

c.351G>A · rs1284844223 · VCV2093101

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000458%, 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 0.83	GERP -3.3, phastCons 1
Overall
CADD	11.36	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000458% European (non-Finnish) · 5/1,092,150 alleles

Filtering AF 0.000134% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.8e-05%

Overall 0.000423% 6/1,417,580 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00184%	54,302
European (non-Finnish)grpmax	0.000458%	218,430

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: DMRT2
Protein: p.Leu117=
Coding: c.351G>A
MANE Select: NM_181872
dbSNP: rs1284844223
Type: single nucleotide variant
Location: chr9:1051964 (GRCh38)
Gene constraint: LOEUF 1.279 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.37
Residue 117: the 'disordered' region

Full DMRT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMRT2 p.Ala112Glu Uncertain significance ★★ ⚠ same type
DMRT2 p.Ala29Ser Uncertain significance ★★ ⚠ same type
DMRT2 p.Asp176Gly Uncertain significance ★★ ⚠ same type
DMRT2 p.Asp48Glu Uncertain significance ★★ ⚠ same type
DMRT2 p.Cys105Tyr Uncertain significance ★★ ⚠ same type
DMRT2 p.Glu60Gln Uncertain significance ★★ ⚠ same type
DMRT2 p.Gly110Asp Uncertain significance ★★ ⚠ same type
DMRT2 p.Gly36Arg 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/dmrt2-p-leu117 (accessed [today's date]).

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