Is SAMD9L p.Ser641Phe (c.1922C>T) pathogenic?

SAMD9L p.Ser641Phe (c.1922C>T) is classified Uncertain significance in SAMD9L (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-09). AlphaMissense: likely benign (0.1869); Absent from gnomAD v4.1.

How common is SAMD9L p.Ser641Phe (c.1922C>T) in the general population?

SAMD9L p.Ser641Phe (c.1922C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SAMD9L p.Ser641Phe (c.1922C>T)?

AlphaMissense predicts likely benign (score 0.1869) — an in-silico prediction, not a clinical call.

SAMD9L p.Ser641Phe

c.1922C>T · rs2116492212 · VCV1337468

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1869 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1869	likely benign
REVEL	0.172	moderately benign-leaning
SaProt	LLR -8.45	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 6.3	phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 1,885 bp · p 3.1e-05 · regional, not allelic
Overall
CADD	21.7	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

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: SAMD9L
Protein: p.Ser641Phe
Coding: c.1922C>T
MANE Select: NM_152703
dbSNP: rs2116492212
Type: single nucleotide variant
Location: chr7:93134050 (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.Ser641= 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-ser641phe (accessed [today's date]).

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