Is FIS1 p.Ser10Phe (c.29C>T) pathogenic?

FIS1 p.Ser10Phe (c.29C>T) is classified Uncertain significance in FIS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-27). AlphaMissense: likely pathogenic (0.7283); Very rare (popmax 0.00223%, eas).

How common is FIS1 p.Ser10Phe (c.29C>T) in the general population?

FIS1 p.Ser10Phe (c.29C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about FIS1 p.Ser10Phe (c.29C>T)?

AlphaMissense predicts likely pathogenic (score 0.7283) — an in-silico prediction, not a clinical call.

FIS1 p.Ser10Phe

c.29C>T · VCV3515431

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7283 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7283	likely pathogenic
REVEL	0.315	indeterminate
SaProt	LLR -8.19	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 4.2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 5,195 bp · p 0.61 · regional, not allelic
Overall
CADD	29.2	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 0.00223% East Asian · 1/44,890 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00136% 22/1,613,940 alleles · very rare exomes 21/1,461,692 · genomes 1/152,248 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,890
European (non-Finnish)	0.00169%	58,998
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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: FIS1
Protein: p.Ser10Phe
Coding: c.29C>T
MANE Select: NM_016068
Type: single nucleotide variant
Location: chr7:101244976 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.66 · 12 PDB
Residue 10: an α-helix; a modified residue (phosphoserine)

Full FIS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FIS1 p.Ala137Val Uncertain significance ★ ⚠ same type
FIS1 p.Arg71Gln Uncertain significance ★ ⚠ same type
FIS1 p.Arg83Trp Uncertain significance ★ ⚠ same type
FIS1 p.Asn48Ser Uncertain significance ★ ⚠ same type
FIS1 p.Glu111Gln Uncertain significance ★ ⚠ same type
FIS1 p.Glu12Lys Uncertain significance ★ ⚠ same type
FIS1 p.Glu24Asp Uncertain significance ★ ⚠ same type
FIS1 p.Glu59Lys 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/fis1-p-ser10phe (accessed [today's date]).

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