Is SAMD9L p.Ser1024Phe (c.3071C>T) pathogenic?

SAMD9L p.Ser1024Phe (c.3071C>T) is classified Uncertain significance in SAMD9L (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-30). AlphaMissense: likely benign (0.1462); Ultra-rare (popmax 0.024%, afr).

How common is SAMD9L p.Ser1024Phe (c.3071C>T) in the general population?

SAMD9L p.Ser1024Phe (c.3071C>T) is ultra-rare (popmax 0.024%, afr) (gnomAD).

What do computational predictors say about SAMD9L p.Ser1024Phe (c.3071C>T)?

AlphaMissense predicts likely benign (score 0.1462) — an in-silico prediction, not a clinical call.

SAMD9L p.Ser1024Phe

c.3071C>T · rs141306896 · VCV2714990

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1462 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1462	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -3.68	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 1.1	GERP 3.4, phastCons 0.044
Regional constraint	o/e 0.96	unconstrained · MANE · 823 bp · p 0.48 · regional, not allelic
Overall
CADD	13.41	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.024% African / African-American · 18/75,024 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00124% 20/1,613,310 alleles · ultra-rare exomes 7/1,461,096 · genomes 13/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,168
Admixed American	0.00167%	59,876
European (non-Finnish)	8.48e-05%	1,179,523

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.Ser1024Phe
Coding: c.3071C>T
MANE Select: NM_152703
dbSNP: rs141306896
Type: single nucleotide variant
Location: chr7:93132901 (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

Similar variants

SAMD9L p.Ser1024= Likely benign ★ same residue
SAMD9L p.Arg986Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
SAMD9L p.His880Gln Pathogenic ★★ ⚠ same type
SAMD9L p.Ala1073Thr Uncertain significance ★★ ⚠ same type
SAMD9L p.Ala1087Asp Uncertain significance ★★ ⚠ same type
SAMD9L p.Ala1087Val Uncertain significance ★★ ⚠ same type
SAMD9L p.Ala1106Thr Uncertain significance ★★ ⚠ same type
SAMD9L p.Ala1106Val 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/samd9l-p-ser1024phe (accessed [today's date]).

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