Is DMRT1 p.Lys103Arg (c.308A>G) pathogenic?

DMRT1 p.Lys103Arg (c.308A>G) is classified Likely benign in DMRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-17). AlphaMissense: likely benign (0.1033); Rare (popmax 0.288%, mid).

How common is DMRT1 p.Lys103Arg (c.308A>G) in the general population?

DMRT1 p.Lys103Arg (c.308A>G) is rare (popmax 0.288%, mid) (gnomAD).

What do computational predictors say about DMRT1 p.Lys103Arg (c.308A>G)?

AlphaMissense predicts likely benign (score 0.1033) — an in-silico prediction, not a clinical call.

DMRT1 p.Lys103Arg

c.308A>G · rs201947617 · VCV2198711

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1033 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.288%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1033	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -6.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP -5.4, phastCons 1
Regional constraint	o/e 1.32	unconstrained · MANE · 316 bp · p 7e-05 · regional, not allelic
Overall
CADD	24.1	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 0.288% Middle Eastern · 17/5,896 alleles

Filtering AF 0.184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.151%

Overall 0.0125% 194/1,547,532 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.288%	347
South Asian	0.0743%	1,345
Remaining individualsnot grpmax-eligible	0.0348%	2,872
European (non-Finnish)	0.00764%	13,083
African / African-American	0.00409%	24,460
Finnishnot grpmax-eligible	0.00207%	48,382
Admixed American	0.00191%	52,368

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: DMRT1
Protein: p.Lys103Arg
Coding: c.308A>G
MANE Select: NM_021951
dbSNP: rs201947617
Type: single nucleotide variant
Location: chr9:842146 (GRCh38)
Gene constraint: LOEUF 0.432 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 57.76 · 1 PDB
Residue 103: a DNA-binding region

Full DMRT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMRT1 p.Asn151Ser Uncertain significance ★★ ⚠ same type
DMRT1 p.Met275Val Uncertain significance ★★ ⚠ same type
DMRT1 p.Ser58Cys Uncertain significance ★★ ⚠ same type
DMRT1 p.Thr366Ser Uncertain significance ★★ ⚠ same type
DMRT1 p.Val265Met Uncertain significance ★★ ⚠ same type
DMRT1 c.355-218G>C Benign ★★ same type
DMRT1 c.355-8G>C Benign ★★ same type
DMRT1 c.538+65A>G Benign ★★ 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/dmrt1-p-lys103arg (accessed [today's date]).

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