Is KDM3A p.Arg692Lys (c.2075G>A) pathogenic?

KDM3A p.Arg692Lys (c.2075G>A) is classified Likely benign in KDM3A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: likely benign (0.053); Ultra-rare (popmax 0.015%, amr).

How common is KDM3A p.Arg692Lys (c.2075G>A) in the general population?

KDM3A p.Arg692Lys (c.2075G>A) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about KDM3A p.Arg692Lys (c.2075G>A)?

AlphaMissense predicts likely benign (score 0.053) — an in-silico prediction, not a clinical call.

KDM3A p.Arg692Lys

c.2075G>A · rs754268475 · VCV3113747

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.053 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.053	likely benign
REVEL	0.24	benign-leaning
SaProt	LLR -5.01	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 -0.24	GERP -5.6, phastCons 0.007
Regional constraint	o/e 0.89	unconstrained · MANE · 6,966 bp · p 0.019 · regional, not allelic
Overall
CADD	10.74	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 0.015% Admixed American · 9/60,008 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00578%

Overall 0.00149% 24/1,614,048 alleles · ultra-rare exomes 20/1,461,872 · genomes 4/152,176 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,668
South Asian	0.0022%	45,545
African / African-American	0.00133%	74,920
European (non-Finnish)	0.00102%	98,336

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: KDM3A
Protein: p.Arg692Lys
Coding: c.2075G>A
MANE Select: NM_018433
dbSNP: rs754268475
Type: single nucleotide variant
Location: chr2:86478012 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 69.06

Full KDM3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KDM3A c.2512+19T>C Benign ★★ same type
KDM3A p.Leu1283= Benign/Likely benign ★★ same type
KDM3A p.Leu937= Benign ★★ same type
KDM3A p.Val63= Likely benign ★★ same type
KDM3A c.1940-2A>G Uncertain significance ★ same type
KDM3A p.Ala307Thr Uncertain significance ★ ⚠ same type
KDM3A p.Ala322Thr Uncertain significance ★ ⚠ same type
KDM3A p.Ala409Val 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/kdm3a-p-arg692lys (accessed [today's date]).

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