Is SAMD9 p.Phe1271Ser (c.3812T>C) pathogenic?

SAMD9 p.Phe1271Ser (c.3812T>C) is classified Likely benign in SAMD9 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-02-01). AlphaMissense: likely pathogenic (0.7972); Rare (popmax 0.716%, sas).

How common is SAMD9 p.Phe1271Ser (c.3812T>C) in the general population?

SAMD9 p.Phe1271Ser (c.3812T>C) is rare (popmax 0.716%, sas) (gnomAD).

What do computational predictors say about SAMD9 p.Phe1271Ser (c.3812T>C)?

AlphaMissense predicts likely pathogenic (score 0.7972) — an in-silico prediction, not a clinical call.

SAMD9 p.Phe1271Ser

c.3812T>C · rs201873378 · VCV735472

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7972 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.716%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7972	likely pathogenic · top 10% in SAMD9
REVEL	0.333	indeterminate
SaProt	LLR -11.99	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 2,122 bp · p 6.9e-06 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.716% South Asian · 651/90,918 alleles

Filtering AF 0.67% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.652%

Overall 0.0442% 712/1,612,544 alleles · rare exomes 675/1,460,336 · genomes 37/152,208 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.716%	140
Remaining individualsnot grpmax-eligible	0.0512%	1,952
Middle Eastern	0.0165%	6,054
Admixed American	0.00667%	14,989
East Asian	0.00446%	22,426
African / African-American	0.00267%	37,506
European (non-Finnish)	0.0017%	58,939

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: SAMD9
Protein: p.Phe1271Ser
Coding: c.3812T>C
MANE Select: NM_017654
dbSNP: rs201873378
Type: single nucleotide variant
Location: chr7:93102286 (GRCh38)
Gene constraint: LOEUF 1.773 · pLI 0.03 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 83.79 · 10 PDB

Full SAMD9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SAMD9 p.Phe1271= Likely benign ★★ same residue
SAMD9 p.Phe1271fs Uncertain significance ★★ same residue
SAMD9 p.Arg1293Trp Pathogenic ★★ ⚠ same type
SAMD9 p.Arg459Gln Pathogenic ★★ ⚠ same type
SAMD9 p.Arg685Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
SAMD9 p.Arg824Gln Pathogenic ★★ ⚠ same type
SAMD9 p.Arg982Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
SAMD9 p.Arg982His Pathogenic/Likely pathogenic ★★ ⚠ 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/samd9-p-phe1271ser (accessed [today's date]).

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