Is TRMT1L p.Ser71Phe (c.212C>T) pathogenic?

TRMT1L p.Ser71Phe (c.212C>T) is classified Uncertain significance in TRMT1L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely benign (0.1123); Very rare (popmax 0.00333%, amr).

How common is TRMT1L p.Ser71Phe (c.212C>T) in the general population?

TRMT1L p.Ser71Phe (c.212C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about TRMT1L p.Ser71Phe (c.212C>T)?

AlphaMissense predicts likely benign (score 0.1123) — an in-silico prediction, not a clinical call.

TRMT1L p.Ser71Phe

c.212C>T · VCV3973955

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1123 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1123	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -9.26	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 7.2	GERP 1.6, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 6,282 bp · p 0.0007 · regional, not allelic
Overall
CADD	25.7	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

Grpmax group 0.00333% Admixed American · 2/60,004 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000558% 9/1,613,800 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,002
Remaining individualsnot grpmax-eligible	0.0016%	62,466
South Asian	0.0011%	91,088
European (non-Finnish)	0.000424%	235,977

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: TRMT1L
Protein: p.Ser71Phe
Coding: c.212C>T
MANE Select: NM_030934
Type: single nucleotide variant
Location: chr1:185156501 (GRCh38)
Gene constraint: LOEUF 0.567 · pLI 0.31 (gnomAD)
Structure: AlphaFold pLDDT 73.62
Residue 71: the 'disordered' region

Full TRMT1L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRMT1L p.Ser71Cys Uncertain significance ★ ⚠ same residue
TRMT1L p.Ala105Val Uncertain significance ★ ⚠ same type
TRMT1L p.Ala120Pro Uncertain significance ★ ⚠ same type
TRMT1L p.Ala120Thr Uncertain significance ★ ⚠ same type
TRMT1L p.Ala271Ser Uncertain significance ★ ⚠ same type
TRMT1L p.Ala385Ser Uncertain significance ★ ⚠ same type
TRMT1L p.Ala443Ser Uncertain significance ★ ⚠ same type
TRMT1L p.Ala444Thr 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/trmt1l-p-ser71phe (accessed [today's date]).

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