Is DMC1 p.Pro287His (c.860C>A) pathogenic?

DMC1 p.Pro287His (c.860C>A) is classified Pathogenic in DMC1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-12-20). AlphaMissense: likely pathogenic (0.9984); Absent from gnomAD v4.1; Associated with azoospermia.

What condition is associated with DMC1 p.Pro287His (c.860C>A)?

DMC1 p.Pro287His (c.860C>A) is associated with azoospermia (ClinVar).

How common is DMC1 p.Pro287His (c.860C>A) in the general population?

DMC1 p.Pro287His (c.860C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DMC1 p.Pro287His (c.860C>A)?

AlphaMissense predicts likely pathogenic (score 0.9984) — an in-silico prediction, not a clinical call.

DMC1 p.Pro287His

c.860C>A · rs2145771075 · VCV1328945

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9984 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

azoospermia

Computational evidence

Protein change
AlphaMissense	0.9984	likely pathogenic ✓ concordant with ClinVar · top 4% in DMC1
REVEL	0.743	pathogenic-leaning
SaProt	LLR -15.21	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Overall
CADD	29.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DMC1
Protein: p.Pro287His
Coding: c.860C>A
MANE Select: NM_030630 · reported on NM_007068
dbSNP: rs2145771075
Type: single nucleotide variant
Location: chr22:38521701 (GRCh38)
Structure: AlphaFold pLDDT 86.13
Residue 287: a UniProt-annotated variant site (in dee105; likely pathogenic)

Full DMC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

azoospermia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DMC1 p.Thr122Ala Pathogenic same condition
HID1 p.Asp201Asn Uncertain significance ★★ ⚠ same type
HID1 p.Ser87Leu Uncertain significance ★★ ⚠ same type
DMC1 p.Met200Val Benign ★★ ⚠ same type
HID1 c.1149+7C>T Benign ★★ same type
HID1 p.Gln130Glu Benign ★★ same type
HID1 p.His192Tyr Benign ★★ same type
HID1 c.1149+1G>T Likely pathogenic ★ 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/dmc1-p-pro287his (accessed [today's date]).

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