Is SAMD9L p.Phe709= (c.2127T>C) pathogenic?

SAMD9L p.Phe709= (c.2127T>C) is classified Benign/Likely benign in SAMD9L (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-08). Rare (popmax 0.606%, afr); Associated with Inborn genetic diseases.

What condition is associated with SAMD9L p.Phe709= (c.2127T>C)?

SAMD9L p.Phe709= (c.2127T>C) is associated with Inborn genetic diseases (ClinVar).

How common is SAMD9L p.Phe709= (c.2127T>C) in the general population?

SAMD9L p.Phe709= (c.2127T>C) is rare (popmax 0.606%, afr) (gnomAD).

SAMD9L p.Phe709=

c.2127T>C · rs7792360 · VCV792083

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.606%, afr)

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 3.3	phastCons 1
Overall
CADD	3.099	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.606% African / African-American · 454/74,952 alleles

Filtering AF 0.56% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.541%

Overall 0.03% 484/1,613,502 alleles · rare exomes 235/1,461,194 · genomes 249/152,308 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.606%	165
Admixed American	0.0234%	4,276
Remaining individualsnot grpmax-eligible	0.0208%	4,804
European (non-Finnish)	0.000254%	393,266

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.Phe709=
Coding: c.2127T>C
MANE Select: NM_152703
dbSNP: rs7792360
Type: single nucleotide variant
Location: chr7:93133845 (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.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
SAMD9L p.Ala1156Glu Uncertain significance ★★ ⚠ same condition
SAMD9L p.Ala1156Ser Uncertain significance ★★ ⚠ same condition
SAMD9L p.Ala1159Pro 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-phe709 (accessed [today's date]).

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