Is SAMD9L p.Asp720= (c.2160T>C) pathogenic?

SAMD9L p.Asp720= (c.2160T>C) is classified Likely benign in SAMD9L (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-20). Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with SAMD9L p.Asp720= (c.2160T>C)?

SAMD9L p.Asp720= (c.2160T>C) is associated with Inborn genetic diseases (ClinVar).

How common is SAMD9L p.Asp720= (c.2160T>C) in the general population?

SAMD9L p.Asp720= (c.2160T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

SAMD9L p.Asp720=

c.2160T>C · VCV4844805

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Inborn genetic diseases

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 -2.7
Overall
CADD	0.149	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,016 alleles

Overall 0.000137% 2/1,461,308 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,016
European (non-Finnish)	8.48e-05%	1,179,816

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: SAMD9L
Protein: p.Asp720=
Coding: c.2160T>C
MANE Select: NM_152703
Type: single nucleotide variant
Location: chr7:93133812 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.85

Full SAMD9L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SAMD9L p.Asp720Ala Uncertain significance ★★ ⚠ same residue
SAMD9L p.Asp720Asn Uncertain significance ★ ⚠ same residue
SAMD9L p.Asp720Glu Uncertain significance ★ ⚠ same residue
SAMD9L p.Ala1073Thr Uncertain significance ★★ ⚠ same condition
SAMD9L p.Ala1087Asp Uncertain significance ★★ ⚠ same condition
SAMD9L p.Ala1106Thr Uncertain significance ★★ ⚠ same condition
SAMD9L p.Ala1106Val Uncertain significance ★★ ⚠ same condition
SAMD9L p.Ala1109Pro Uncertain significance ★★ ⚠ same condition

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/samd9l-p-asp720 (accessed [today's date]).

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