Is FDFT1 p.Ser102Cys (c.305C>G) pathogenic?

FDFT1 p.Ser102Cys (c.305C>G) is classified Uncertain significance in FDFT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-18). AlphaMissense: likely benign (0.0928); Rare (popmax 0.103%, amr).

How common is FDFT1 p.Ser102Cys (c.305C>G) in the general population?

FDFT1 p.Ser102Cys (c.305C>G) is rare (popmax 0.103%, amr) (gnomAD).

What do computational predictors say about FDFT1 p.Ser102Cys (c.305C>G)?

AlphaMissense predicts likely benign (score 0.0928) — an in-silico prediction, not a clinical call.

FDFT1 p.Ser102Cys

c.305C>G · VCV3350386

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0928 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.103%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0928	likely benign
REVEL	0.448	indeterminate
SaProt	LLR -8.89	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4	GERP 1.9, phastCons 0.88
Regional constraint	o/e 1.77	unconstrained · MANE · 36 kb · p 1.6e-69 · regional, not allelic
Overall
CADD	23.1	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 0.103% Admixed American · 62/60,022 alleles

Filtering AF 0.0826% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0752%

Overall 0.0427% 689/1,614,188 alleles · rare exomes 632/1,461,854 · genomes 57/152,334 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.103%	968
Finnishnot grpmax-eligible	0.0547%	1,830
European (non-Finnish)	0.0467%	2,142
Ashkenazi Jewishnot grpmax-eligible	0.0338%	2,961
Remaining individualsnot grpmax-eligible	0.0336%	2,977
East Asian	0.0156%	6,413
African / African-American	0.004%	25,015

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: FDFT1
Protein: p.Ser102Cys
Coding: c.305C>G
MANE Select: NM_004462
Type: single nucleotide variant
Location: chr8:11809774 (GRCh38)
Gene constraint: LOEUF 1.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.14 · 32 PDB
Residue 102: an α-helix

Full FDFT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FDFT1 c.100-85G>C Uncertain significance ★★ same type
FDFT1 p.Ala333Ser Uncertain significance ★★ ⚠ same type
FDFT1 p.Asn265Ser Uncertain significance ★★ ⚠ same type
FDFT1 p.Gly151Asp Uncertain significance ★★ ⚠ same type
FDFT1 p.Ile252Thr Uncertain significance ★★ ⚠ same type
FDFT1 p.Phe210Leu Uncertain significance ★★ ⚠ same type
FDFT1 c.100-179C>G Likely benign ★★ same type
FDFT1 c.1033-25T>C Benign ★★ 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/fdft1-p-ser102cys (accessed [today's date]).

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