Is TTL p.Ile201= (c.603C>T) pathogenic?

TTL p.Ile201= (c.603C>T) is classified Benign in TTL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2017-09-08). Common (popmax 59.2%, eas) — too common for a highly-penetrant pathogenic allele.

TTL p.Ile201=

Q: How common is TTL p.Ile201= (c.603C>T) in the general population?

TTL p.Ile201= (c.603C>T) is common (popmax 59.2%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.603C>T · rs2918763 · VCV770130

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 59.2%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.008	GERP -3.3, phastCons 0.78
Overall
CADD	12.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 59.2% East Asian · 23,977/40,528 alleles

Filtering AF 58.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 58.3%

Overall 32.6% 415,136/1,272,662 alleles · common exomes 357,521/1,127,182 · genomes 57,615/145,480 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	59.2%	2
Finnishnot grpmax-eligible	48%	2
Amishnot grpmax-eligible	45.4%	2
South Asian	41.8%	2
African / African-American	41.2%	2
Admixed American	37%	3
Remaining individualsnot grpmax-eligible	33.9%	3
European (non-Finnish)	28.8%	3
Ashkenazi Jewishnot grpmax-eligible	28.1%	4
Middle Eastern	25.8%	4

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: TTL
Protein: p.Ile201=
Coding: c.603C>T
MANE Select: NM_153712
dbSNP: rs2918763
Type: single nucleotide variant
Location: chr2:112501339 (GRCh38)
Gene constraint: LOEUF 0.423 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.13 · 1 PDB
Residue 201: the ttl domain; a β-strand

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

Similar variants

TTL c.237-9A>T Benign ★★ same type
TTL p.Ala133Thr Benign ★★ same type
TTL p.Asn145= Benign ★★ same type
TTL p.Ala133Val Uncertain significance ★ ⚠ same type
TTL p.Arg197His Uncertain significance ★ ⚠ same type
TTL p.Arg29Lys Uncertain significance ★ ⚠ same type
TTL p.Arg44Lys Uncertain significance ★ ⚠ same type
TTL p.Arg46Trp 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/ttl-p-ile201 (accessed [today's date]).

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