Is AMDHD2 c.970+10C>T pathogenic?

AMDHD2 c.970+10C>T is classified Uncertain significance in AMDHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-29). Very rare (popmax 0.00801%, afr).

How common is AMDHD2 c.970+10C>T in the general population?

AMDHD2 c.970+10C>T is very rare (popmax 0.00801%, afr) (gnomAD).

AMDHD2 c.970+10C>T

VCV4640177

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.115	moderately benign-leaning
Splicing
Splice region	donor +10	near-intronic (+10 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.38	GERP -0.97
Overall
CADD	3.738	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,928 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000372% 6/1,612,504 alleles · very rare

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: AMDHD2
Coding: c.970+10C>T
MANE Select: NM_001330449
Type: single nucleotide variant
Location: chr16:2528569 (GRCh38)
Gene constraint: LOEUF 0.868 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.49 · 2 PDB

Full AMDHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATP6V0C p.Pro49Leu Likely pathogenic ★★ same type
ATP6V0C p.Ala95Thr Likely pathogenic ★ same type
AMDHD2 c.970+19T>G Uncertain significance ★ same type
AMDHD2 c.970+40C>T Uncertain significance ★ same type
AMDHD2 c.970+7G>A Uncertain significance ★ same type
AMDHD2 c.971-18G>A Uncertain significance ★ same type
AMDHD2 c.971-27C>G Uncertain significance ★ same type
AMDHD2 c.971-31C>T 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/amdhd2-c-970-plus-10c-t (accessed [today's date]).

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